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1.
Mol Med Rep ; 23(2): 1, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33655328

RESUMO

Immunoglobulin (Ig) A, an antibody with a pivotal role in gut homeostasis, can be modulated by stress and bovine lactoferrin (bLf). The aim of the present study was to analyze the impact of chronic stress on the IgA response in the small intestine during bLf treatment. Male BALB/c mice (n=6 mice/group) underwent 1 h of chronic stress by immobilization for 7 consecutive days or were left unstressed, and were untreated or treated with bLf (50, 500 or 5,000 µg). Plasma corticosterone expression levels were determined by ELISA. The distal small intestine was dissected to analyze: i) total IgA, secretory IgA and IgG, as well as and specific IgA and IgG antibody levels in the intestinal liquid by ELISA; ii) α­chain and polymeric immunoglobulin receptor (pIgR) protein expression in epithelial cell extracts analyzed by western blotting; iii) the mRNA expression levels of α­/J­chains, pIgR, IL­2, IL­4, IL­5 and IL­6 in whole mucosal samples by reverse transcription­quantitative PCR. Data were analyzed by one­way ANOVA, and the differences were analyzed by the Holm­Sidák post hoc test and were considered significant if P<0.05. Results from the present study revealed the upregulatory effects of chronic stress on the total antibody levels, protein (α­chain; 78­kDa pIgR) and mRNA (α­ and J­chains; pIgR; IL­6) expression levels were restricted by bLf under stress. The effects of chronic stress on the downregulation of IL­2 and IL­4 mRNA expression were not changed by bLf under stress. The corticosterone response in unstressed mice treated with 5,000 µg bLf and the specific­IgG levels in the unstressed and stressed groups treated with bLf at all doses were increased. The findings suggested an effect of bLf in maintaining homeostasis under stress.


Assuntos
Corticosterona/sangue , Intestino Delgado/metabolismo , Lactoferrina/farmacologia , Estresse Psicológico/tratamento farmacológico , Animais , Regulação da Expressão Gênica , Imunoglobulina A/análise , Imunoglobulina A/genética , Imunoglobulina A Secretora/análise , Imunoglobulina A Secretora/genética , Imunoglobulina G/análise , Imunoglobulina G/genética , Intestino Delgado/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Estresse Psicológico/sangue , Estresse Psicológico/imunologia
2.
J Korean Med Sci ; 36(4): e28, 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33496087

RESUMO

Hospitalized coronavirus disease 2019 (COVID-19)-infected patients suffer from both physical impairments and mental stress. Respiratory insufficiency and cardiovascular disturbances require most of the intensive care interventions, but they are also accompanied by depressive conditions, sadness and fear of dying. Sedatives are mostly respiratory and cardiovascular depressants and do not provide resistance to the pro-inflammatory burst induced by the virus. Ketamine is a unique and safe drug that enables well-controlled sedation and anesthesia, attenuates depression and mitigates suicidal thoughts, without depressing respiratory or cardiovascular mechanics. This brief communication highlights the benefits potentially provided by ketamine to patients hospitalized for COVID-19 infection.


Assuntos
/tratamento farmacológico , Depressão/tratamento farmacológico , Ketamina/uso terapêutico , Estresse Psicológico/tratamento farmacológico , Anestesia , Ansiedade/tratamento farmacológico , Cuidados Críticos , Depressão/complicações , Hemodinâmica , Hospitalização , Humanos , Hipnóticos e Sedativos , Sistema Imunitário , Insuficiência Respiratória , Estresse Psicológico/complicações , Ideação Suicida , Resultado do Tratamento
3.
Int J Mol Sci ; 22(2)2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33477830

RESUMO

The forced swim stress test (FST) is widely used for screening pharmacological or non-pharmacological strategies with potential antidepressant activities. Recent data have suggested that repeated FST for five consecutive days (i.e., 5d-RFSS) could be used to generate a robust depressive-like phenotype in mice. However, the face, construct, and predictive validities of 5d-RFSS have been recently challenged. This study took advantage of recent findings showing that mice vulnerability to anxiety is enhanced when animals are stressed during the dark phase, to provide new insight into the relevance of this model. Our results showed a progressive increase in time of immobility in 5d-RFSS mice relative to control non-stressed animals (sham). Three weeks later, we noticed that 5d-RFSS mice injected with the vehicle compound (Veh) still exhibited a high level of immobility in the FST whereas this behavior was reversed by the antidepressant drug amitriptyline (AMI). However, 5d-RFSS/Veh and 5d-RFSS mice/AMI mice showed normal performances in the open field, the novelty suppressed feeding and the tail suspension tests. Despite this lack of generalized behavioral deficits, an impairment of different parameters characterizing the hypothalamic-pituitary-adrenal (HPA) axis reactivity was evidenced in 5d-RFSS mice/Veh but not in 5d-RFSS mice/AMI. Despite anomalies in the HPA axis, the activity of the central serotonergic system remained unaffected in 5d-RFSS mice relative to controls. From our results, it is suggested that learned immobility does not replicate the broad spectrum of depressive symptoms observed in other chronic models of depression such as the unpredictable chronic mild stress (UCMS) model, the chronic social defeat stress (CSDS) model or chronic corticosterone (CORT) exposure but its influence on the HPA axis is remarkable. Further experiments are warranted to makes this model suitable for modelling depression and therefore refine its translational applicability.


Assuntos
Ansiedade/tratamento farmacológico , Corticosterona/farmacologia , Transtorno Depressivo/tratamento farmacológico , Estresse Psicológico/tratamento farmacológico , Animais , Antidepressivos/farmacologia , Ansiedade/fisiopatologia , Transtornos de Ansiedade/tratamento farmacológico , Transtornos de Ansiedade/patologia , Comportamento Animal/efeitos dos fármacos , Transtorno Depressivo/patologia , Modelos Animais de Doenças , Humanos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/patologia , Camundongos , Fenótipo , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/patologia , Estresse Psicológico/patologia , Natação
4.
J Ethnopharmacol ; 266: 113283, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32827659

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Zhi-zi-chi decoction (ZZCD) is used for treating depression as an effectively traditional Chinese medicine. Until now, studies on pharmacological research of ZZCD have mostly been centered in pharmacokinetic level. Little was known about its pharmacological mechanism of relieving depression. AIM OF THE STUDY: This study was to evaluate the effect of ZZCD on relieving depression via behavioral tests, serum metabolomics and signaling target expression analysis on chronic unpredictable mild stress (CUMS) model mice. MATERIALS AND METHODS: The CUMS exposure lasted 7 consecutive weeks. The mice were administrated with ZZCD for the last 3 weeks. Behavioral tests were applied and a serum metabolomics method based on UFLC/Q-TOF-MS with multivariate statistical and global metabolic network analysis was performed to identify relevant metabolites and pathways. Finally, the protein expressions in mouse hippocampi were determined by western blot to verify the metabolomics deduction. RESULTS: Behavioral parameters were visibly changed after modeling, while high and medium dosage groups showed status improvement compared to the model group. Seventy six metabolites were identified as potential biomarkers from the metabolomics profiles in C18 and HILIC systems. In addition, 9 significant pathways related to changed biomarkers were conducted. The pathways were closely connected by some key targets, which were significantly reduced in the model group compared with those in control group, while ZZCD treated groups showed corrections after 3-week administration. The results revealed that the anti-depression efficacy of ZZCD might be associated with PKA-CREB-BDNF-TrkB-PSD-95 pathway influenced by metabolic changes, verifying the pathway annotation speculation. CONCLUSION: This study demonstrated that ZZCD had a positive treatment effect on CUMS depression model mice. Metabolomics results revealed the holistic and interconnected metabolic changes of ZZCD in CUMS mice. The metabolic pathway annotation suggested that the anti-depression mechanism of ZZCD might be related to signaling pathway in brain. PKA-CREB-BDNF-TrkB-PSD-95 signaling expression was a verification and complement to the metabolomics results.


Assuntos
Antidepressivos/farmacologia , Depressão/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Estresse Psicológico/tratamento farmacológico , Animais , Antidepressivos/isolamento & purificação , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Modelos Animais de Doenças , Masculino , Medicina Tradicional Chinesa , Metabolômica , Camundongos , Camundongos Endogâmicos BALB C , Transdução de Sinais/efeitos dos fármacos
5.
J Ethnopharmacol ; 265: 113395, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32956757

RESUMO

ETHNOPHARMACOLOGY RELEVANCE: Armillaria mellea (Vahl) P. Kumm. (AM) is an edible mushroom that has been reported as treatment for several neurological disorders, such as dizziness and epilepsy in Asia. Importantly, AM shares a symbiotic relationship with Gastrodia elata Blume (GE), a medicinal herb with antidepressant-like properties. Researchers believe that AM may possess pharmacological properties similar to GE due to their symbiosis, however, few studies have investigated the pharmacological effect of AM. AIM OF THE STUDY: The aim of this study was to explore the potential of AM as an antidepressant in forced-swimming test (FST) and unpredictable chronic mild stress (UCMS) rodent models and investigate its possible underlying mechanism. MATERIALS AND METHODS: Rats were orally administrated with 250, 500, and 1000 mg/kg body weight (bw) water extract of AM (WAM) for 28 and 35 consecutive days prior to the FST and UCMS protocols, respectively. The cerebral serotonin (5-HT) and the metabolites in the frontal cortex of rats were measured. The brain was dissected and the blood was collected to investigate the levels of inflammatory-related signaling pathway. RESULTS: All doses of WAM reduced the immobility time in the FST without disturbing autonomic locomotion. All doses of WAM prevented stress-induced abnormal behaviors in the UCMS model, including decreased sucrose preference and hypoactivity. 500 and 1000 mg/kg bw WAM attenuated the stress-induced increases in IL-1ß and TNF-α in the serum and cerebrum. 1000 mg/kg bw WAM alleviated brain inflammation by reducing the protein expression of ionized calcium binding adaptor molecule 1. CONCLUSION: WAM exhibited acute and chronic antidepressant-like effects, and may result from the anti-inflammatory actions. Therefore, the development of AM as a dietary therapy or adjuvant for depression treatment should be considered.


Assuntos
Anti-Inflamatórios/farmacologia , Antidepressivos/farmacologia , Armillaria/química , Depressão/tratamento farmacológico , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/isolamento & purificação , Antidepressivos/administração & dosagem , Antidepressivos/isolamento & purificação , Comportamento Animal/efeitos dos fármacos , Depressão/fisiopatologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Inflamação/tratamento farmacológico , Inflamação/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Serotonina/metabolismo , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/fisiopatologia , Natação , Água
6.
J Ethnopharmacol ; 265: 113441, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33027642

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Kyung-Ok-Ko (KOK), a traditional medicinal formula composed of Rehmannia glutinosa (Gaertn.) DC, Poria cocos (Schw.) Wolf, Korean Red Panax ginseng C.A.Mey, and honey, has been used to treat amnesia and dementia. KOK has also been shown to ameliorate transient cerebral global ischemia-induced brain damage, but the antidepressant-like effect of KOK has not been examined. AIM OF THE STUDY: This study examined the antidepressant-like effect of KOK in an immobilization-induced stress mouse and its mechanisms of action. MATERIALS AND METHODS: The animals in the stress group were immobilized for two hours a day for two weeks. KOK at a dose of 1 g/kg/day was administered orally to the stressed mice for two weeks in advance of their immobilization. A forced swimming test was performed to analyze their depressive behaviors. To examine the anti-inflammatory or antioxidative effects of KOK, the murine macrophage cell line, RAW 264.7 cells and human neuroblastoma cell, SH-SY5Y cells, were treated with lipopolysaccharide (LPS) and hydrogen peroxide, respectively. RESULT: The KOK extract showed no significant toxicity when the cells were treated with a KOK extract at 5, 10, 25, 50, and 100 µg/mL. The KOK ethanol extract reduced LPS-induced TNF-α production, inducible nitric oxide (iNOS) mRNA level, and the levels of MAPK and p38 phosphorylation in RAW 264.7 cells. KOK also suppressed H2O2-induced cell death and the production of reactive oxygen species (ROS) in SH-SY5Y cells. In the forced swimming test, KOK induced a decrease in immobility and an increase in climbing activity. Finally, the administration of KOK reversed the up-regulation of IkB-α phosphorylation in the stressed mouse cortex. CONCLUSION: KOK might be useful for the treatment of depression caused by environmental and lifestyle-related stress.


Assuntos
Depressão/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Inflamação/tratamento farmacológico , Estresse Psicológico/tratamento farmacológico , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/toxicidade , Antidepressivos/administração & dosagem , Antidepressivos/farmacologia , Antidepressivos/toxicidade , Comportamento Animal/efeitos dos fármacos , Linhagem Celular Tumoral , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/toxicidade , Humanos , Inflamação/patologia , Lipopolissacarídeos , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Óxido Nítrico/metabolismo , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo
7.
J Ethnopharmacol ; 265: 113317, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32861821

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Radix Polygalae (RP) has been traditionally used for the treatment of various psychiatric disorders in East Asia. AIM OF THE STUDY: Depression is a severe mental disease with high prevalence in people, and neurobiology changes of depression are not fully clarified yet. The present study aimed to investigate the antidepressant effect and underlying mechanism of RP in behavioral despair mice and chronic restraint stress (CRS)-induced rats. MATERIALS AND METHODS: ICR mice were treated with various doses of RP (0.13-1.0 g/kg) for 14 days and then subjected to forced swimming test (FST). Wistar rats were exposed to 6-hour restraint stress daily for 28 days, and RP (0.5 and 1 g/kg) was administered by gavage 1 h prior to CRS procedure. Subsequently, behavioral tests were performed and brains were collected for biochemical analysis. RESULTS: RP reduced immobility time of mice in FST and reversed abnormal behaviors of rats induced by CRS in sucrose preference test, novelty-suppressed feeding test, open field test and FST. Moreover, RP could enhance the expression of LC3-II and beclin1 and decrease the level of p62 both in cortex of mice and prefrontal cortex (PFC) of rats, and regulate the dysfunction of AMPK-mTOR pathway in PFC of CRS rats. Activated microglia, impaired astrocyte, elevated protein expression of NLRP3, ASC and caspase-1, and increased mRNA levels of proinflammatory cytokines were observed in PFC of CRS rats, all of which were corrected by RP treatment. CONCLUSION: RP exerted remarkable antidepressant activity in behavioral despair mice and CRS-induced rats, probably by promoting autophagy and inhibiting neuroinflammation.


Assuntos
Antidepressivos/farmacologia , Depressão/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Estresse Psicológico/tratamento farmacológico , Animais , Antidepressivos/administração & dosagem , Autofagia/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos ICR , Ratos , Ratos Wistar , Restrição Física , Natação
8.
Int J Mol Sci ; 21(24)2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33348553

RESUMO

As daily lifestyle is closely associated with mental illnesses, diet-based preventive approaches are receiving attention. Supplementation with hop bitter acids such as iso-α-acids (IAA) and mature hop bitter acids (MHBA) improves mood states in healthy older adults. However, the underlying mechanism remains unknown. Since acute oral consumption with IAA increases dopamine levels in hippocampus and improves memory impairment via vagal nerve activation, here we investigated the effects of chronic administration of hop bitter acids on the dopaminergic activity associated with emotional disturbance in a mouse model of repeated social defeat stress (R-SDS). Chronic administration of IAA and MHBA significantly increased dopaminergic activity based on the dopamine metabolite to dopamine ratio in the hippocampus and medial prefrontal cortex following R-SDS. Hippocampal dopaminergic activity was inversely correlated with the level of R-SDS-induced social avoidance with or without IAA administration. Therefore, chronic treatment with hop bitter acids enhances stress resilience-related hippocampal dopaminergic activity.


Assuntos
Cicloexenos/administração & dosagem , Dopamina/metabolismo , Hipocampo/metabolismo , Humulus/química , Extratos Vegetais/administração & dosagem , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/metabolismo , Terpenos/administração & dosagem , Sintomas Afetivos/tratamento farmacológico , Animais , Comportamento Animal/efeitos dos fármacos , Cicloexenos/química , Modelos Animais de Doenças , Isomerismo , Masculino , Memória/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Extratos Vegetais/química , Terpenos/química
10.
Life Sci ; 258: 118107, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32682919

RESUMO

Cognitive impairment has been widely recognized as a common symptom of chronic stress. Ginsenoside Rd (GRd), the major active compound in Panax ginseng, was previously reported in various neurological researches. However, little research is available regarding on the effect of GRd on cognitive improvement in mice subjected to chronic stress. In the present study, we investigated the neuroprotective effects of GRd in chronic restraint stress (CRS)-induced cognitive deficits and explored the potential mechanism in male C57BL/6J mice. Our results demonstrated that oral administration of GRd for 28 days markedly increased the spontaneous alternation in Y-maze and the relative discrimination index in novel object or location recognition tests following CRS. Additionally, GRd treatment considerably increased the antioxidant enzymes activities in the hippocampus. The expression levels of hippocampus and serum inflammation factors in the CRS groups were also counter-regulated by GRd treatment. Meanwhile, GRd treatment could reverse CRS-induced the decrease in phosphorylated phosphoinositide 3-kinase (PI3K), camp-reflecting element binding protein (CREB), brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) expression in the hippocampus. These findings provided evidences that GRd improves cognitive impairment in CRS mice by mitigating oxidative stress and inflammation, while upregulating the hippocampal BDNF-mediated CREB signaling pathway.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Ginsenosídeos/uso terapêutico , Restrição Física , Transdução de Sinais , Estresse Psicológico/tratamento farmacológico , Animais , Doença Crônica , Disfunção Cognitiva/sangue , Disfunção Cognitiva/fisiopatologia , Modelos Animais de Doenças , Ginsenosídeos/química , Ginsenosídeos/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/enzimologia , Hipocampo/patologia , Hipocampo/fisiopatologia , Inflamação/sangue , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória de Curto Prazo/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Modelos Biológicos , Atividade Motora/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Receptor trkB/metabolismo , Transdução de Sinais/efeitos dos fármacos , Estresse Psicológico/sangue , Estresse Psicológico/fisiopatologia
11.
Riv Psichiatr ; 55(3): 145-151, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32489191

RESUMO

INTRODUCTION: Peritraumatic distress is an important predictor of post-traumatic stress disorder and although several questionnaires are available for its measurement, none of these are specific to CoViD-19. The new CoViD-19 Peritraumatic Distress Index (CPDI), developed in China, is characterized as a rapid compilation tool (10 minutes), easily understandable and appreciated by people. AIM: The objectives of this study were: (1) the validation of the Italian version of the CPDI, and (2) the measurement of the prevalence of peritraumatic distress in this phase 1 CoViD-19. METHOD: CPDI has been translated using a standard forward-backward-translation procedure and offered online to 329 people (191 females and 137 males, aged 46.49 ± 13.58 years). The CPDI showed an internal-consistency of Cronbach's α =0.916. Content validity was judged satisfactory by two psychologists experienced in stress and trauma. The construct validity is given by the high correlation with the dimensions of Intrusion, Avoidance and Hyperarousal as measured by the Impact of Event Scale-Revised (r=0.63, r=0.57, r=0.71, respectively). RESULTS: Our results are comparable to the Chinese ones. A third of people experienced symptoms of mild/moderate and severe peritraumatic distress. Females have higher scores, compared to males. Older people are more resilient, compared to younger, and those who have been in quarantine report less distress than those didn't, as evidenced by the results of the multivariate logistic regression model. High distress was associated with use of psychotropic drugs (AOR=4.28; 95% CI=1.55-11.85), sleeping remedies (AOR=4.05; 95% CI=2.07-7.94), be worried about dying in case of contagion CoViD-19 (AOR=3.33; 95% CI=1.83-6.06), female gender (AOR=2.95; 95% CI=1.58-5.53) and have a religious belief (AOR=1.97; 95% CI=1.05-3.70). To be aged 51-71 years, to have been in quarantine and to have received psychological support were variables associated with lower distress scores. CONCLUSIONS: The psychometric properties of the Italian version are satisfactory and confirm that CPDI is a tool fast, non-intrusive, administered online, and therefore 'safe' in a phase with a high risk of contagion. It allows, like a psychic thermoscan, to quickly detect the needs of the population and propose equally rapid interventions.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/psicologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/psicologia , Testes Psicológicos , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Estresse Psicológico/diagnóstico , Adulto , Fatores Etários , Idoso , Atitude Frente a Morte , Feminino , Humanos , Itália , Idioma , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pandemias , Dados Preliminares , Prevalência , Psicometria , Reprodutibilidade dos Testes , Resiliência Psicológica , Fatores Sexuais , Transtornos de Estresse Pós-Traumáticos/etiologia , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/epidemiologia , Traduções , Adulto Jovem
12.
Psychopharmacology (Berl) ; 237(7): 2031-2042, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32388622

RESUMO

RATIONALE: Cocaine use disorder (CUD) is associated with dysregulation of the hypothalamic-pituitary-adrenal axis, which plays a critical role in the human stress response. Men and women with CUD differ in reactivity to social stressors. The hypothalamic neuropeptide oxytocin is involved in anxiolytic and natural reward processes, and has shown therapeutic potential for addictive disorders and stress reduction. OBJECTIVES: To examine the impact of oxytocin (oxytocin (OXY) vs. placebo (PBO)) and gender (female (F) vs. male (M)) on response to a social stress task in individuals with CUD. To explore whether ovarian hormones moderate this stress response. METHODS: One hundred twelve adults with CUD were randomized to receive 40 IU intranasal oxytocin (n = 56) or matching placebo (n = 56). Forty minutes after drug administration, participants were exposed to a social stressor. Generalized linear mixed models were used to examine neuroendocrine (cortisol) and subjective (craving, stress) response at pre-stressor, stressor + 0, + 10, + 30, + 60 min. RESULTS: Gender moderated the effect of oxytocin on neuroendocrine response (p = 0.048); women receiving oxytocin (F + OXY) showed blunted cortisol response compared to the other three groups (F + PBO; M + OXY; M + PBO). There was a main effect of gender on subjective stress response; women reported greater stress following the stressor compared to men (p = 0.016). Oxytocin had no significant effect on craving or stress, and gender did not moderate the effect of oxytocin on either measure. Higher endogenous progesterone was associated with lower craving response in women (p = 0.033). CONCLUSIONS: Oxytocin may have differential effects in men and women with CUD. Women may be at greater risk for relapse in response to social stressors, but ovarian hormones may attenuate this effect.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/tratamento farmacológico , Hormônios Esteroides Gonadais/sangue , Ovário/metabolismo , Ocitocina/administração & dosagem , Caracteres Sexuais , Estresse Psicológico/tratamento farmacológico , Administração Intranasal , Adulto , Transtornos Relacionados ao Uso de Cocaína/sangue , Método Duplo-Cego , Estradiol/sangue , Feminino , Humanos , Hidrocortisona/sangue , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Pessoa de Meia-Idade , Ovário/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/metabolismo , Progesterona/sangue , Estresse Psicológico/sangue , Resultado do Tratamento , Adulto Jovem
13.
Oxid Med Cell Longev ; 2020: 2325391, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32273940

RESUMO

Depression is an inflammatory-related condition, with the progression in neuronal damage resulting in major depression disorder. Ginsenoside-Rg1, a sterol extract from the herb Panax ginseng, has been shown to exert neuroprotective effects upon neurodegeneration disorders. However, whether ginsenoside-Rg1 confers antidepressant-like effects on neuroinflammation as associated with depression, as well as the possible mechanism involved in these neuroprotective effects, is currently unclear. In the present report, we show that treatment with ginsenoside-Rg1 (40 mg/kg, i.p.) significantly ameliorated depressive-like behaviors as induced by chronic unpredictable mild stress (CUMS) in a rat model of depression. Moreover, these CUMS rats treated with ginsenoside-Rg1 showed reductions in the levels of the oxidative stress products and the activity in the antioxidant stress kinase. Furthermore, CUMS rats treated with ginsenoside-Rg1 showed ameliorated neuroinflammation and associated neuronal apoptosis along with a reduction in dendritic spine atrophy and display of depressive behaviors. Taken together, the results of this study suggest that ginsenoside-Rg1 produces antidepressant-like effects in CUMS-exposed rats; and one of the mechanisms for these antidepressant-like effects of ginsenoside-Rg1 appears to involve protection against oxidative stress and thus the neuronal deterioration resulting from inflammatory responses. These findings provide evidence for the therapeutic potential of ginsenoside-Rg1 in the treatment of stress-related depression.


Assuntos
Depressão/tratamento farmacológico , Ginsenosídeos/uso terapêutico , Inflamação/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Estresse Psicológico/tratamento farmacológico , Animais , Modelos Animais de Doenças , Masculino , Ratos , Ratos Wistar
14.
Phytother Res ; 34(9): 2408-2418, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32281712

RESUMO

Prenatal stress (PS) can lead to impaired spatial learning and memory in offspring. Imperatorin (IMP) is a naturally occurring furanocoumarin with many pharmacological properties. However, the effects of IMP on cognitive impairment induced by PS and the underlying molecular mechanisms remain unclear. We investigated the protective effect of IMP treatment after PS on learning and memory deficits in female offspring at postnatal 60 days. After treating prenatally-stressed offspring with IMP (15 and 30 mg/kg) for 28 days, we found that IMP increased body weight and ameliorated spatial learning and memory and working memory deficits in female offspring rats. Meanwhile, hippocampal Glu and serum corticosterone levels in prenatally-stressed offspring were significantly decreased after IMP administration. Additionally, IMP treatment significantly increased BDNF, TrkB, CaMKII, and CREB mRNA expression in the hippocampus of offspring rats. Furthermore, PS-mediated induction of RKIP protein and mRNA expression and glucocorticoid receptor protein expression in the hippocampus of offspring rats were significantly decreased by IMP treatment, and the protein expression of BDNF and TrkB and relative levels of p-EKR/ERK, p-CaMKIIα/CaMKIIα, and p-CREB/CREB were remarkably increased after IMP treatment. Taken together, IMP can ameliorate PS-induced learning and memory deficits through BDNF/TrkB and ERK/CaMKIIα/CREB signaling pathway and hypothalamic-pituitary-adrenal axis.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/efeitos dos fármacos , Furocumarinas/química , Aprendizagem/efeitos dos fármacos , Transtornos da Memória/tratamento farmacológico , Estresse Psicológico/tratamento farmacológico , Animais , Feminino , Gravidez , Ratos
15.
Psychopharmacology (Berl) ; 237(7): 1973-1987, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32313981

RESUMO

RATIONALE: Obsessive-compulsive disorder (OCD) is characterized by repetitive behaviors exacerbated by stress. Many OCD patients do not respond to available pharmacotherapies, but neurosurgical ablation of the anterior cingulate cortex (ACC) can provide symptomatic relief. Although the ACC receives noradrenergic innervation and expresses adrenergic receptors (ARs), the involvement of norepinephrine (NE) in OCD has not been investigated. OBJECTIVE: To determine the effects of genetic or pharmacological disruption of NE neurotransmission on marble burying (MB) and nestlet shredding (NS), two animal models of OCD. METHODS: We assessed NE-deficient (Dbh -/-) mice and NE-competent (Dbh +/-) controls in MB and NS tasks. We also measured the effects of anti-adrenergic drugs on NS and MB in control mice and the effects of pharmacological restoration of central NE in Dbh -/- mice. Finally, we compared c-fos induction in the locus coeruleus (LC) and ACC of Dbh -/- and control mice following both tasks. RESULTS: Dbh -/- mice virtually lacked MB and NS behaviors seen in control mice but did not differ in the elevated zero maze (EZM) model of general anxiety-like behavior. Pharmacological restoration of central NE synthesis in Dbh -/- mice completely rescued NS behavior, while NS and MB were suppressed in control mice by anti-adrenergic drugs. Expression of c-fos in the ACC was attenuated in Dbh -/- mice after MB and NS. CONCLUSION: These findings support a role for NE transmission to the ACC in the expression of stress-induced compulsive behaviors and suggest further evaluation of anti-adrenergic drugs for OCD is warranted.


Assuntos
Comportamento Compulsivo/metabolismo , Modelos Animais de Doenças , Norepinefrina/metabolismo , Transtorno Obsessivo-Compulsivo/metabolismo , Estresse Psicológico/metabolismo , Antagonistas de Receptores Adrenérgicos alfa 1/farmacologia , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Animais , Comportamento Compulsivo/tratamento farmacológico , Comportamento Compulsivo/psicologia , Feminino , Masculino , Camundongos , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Knockout , Norepinefrina/antagonistas & inibidores , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Transtorno Obsessivo-Compulsivo/psicologia , Receptores Adrenérgicos/metabolismo , Roedores , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/psicologia
16.
Life Sci ; 252: 117669, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32298740

RESUMO

Chronic social defeat stress (CSDS) is an ethologically relevant psychosocial stress animal model and has been widely used in depression studies. Ginsenoside Rg1 (Rg1) is the major active ingredients of ginseng with low toxicity and neuroprotective effects. The present study aims to investigate the antidepressant effects of Rg1 in CSDS mice and explore its molecular mechanism. We found that Rg1 (20 or 40 mg/kg, i.g.) administration significantly alleviated depressive-like behaviors caused by 4-week CSDS exposure, as measured by social interaction test and sucrose preference test, tail suspension test and forced swim test. Additionally, Rg1 treatment inhibited CSDS-induced production of IL-6, TNF-α and IL-1ß, decreased the expression of iNOS, COX2, and caspase-9 and -3, and inhibited microglial activation (Iba1) in the hippocampus. Rg1 was found to significantly downregulate p-JNK1/2 and p-P38 MAPK levels, upregulate p-ERK1/2 levels and inhibit the expression of phosphorylated NF-κB in the hippocampus. Meanwhile, Rg1 regulated SIRT1 and decreased the levels of acetylated p65 (ac-p65) in the hippocampus. Moreover, the reduction in adult hippocampal neurogenesis in CSDS mice was reversed by Rg1 treatment. In conclusion, our findings suggest that Rg1 prevents depressive-like behavior in CSDS-exposed mice, partially through the downregulation of hippocampal neuroinflammation and the upregulation of adult hippocampal neurogenesis and that these changes presumably occur through increased anti-inflammatory effects and the inhibition of proinflammatory cytokine and neurotoxic mediator expression and microglial activation, which is partly mediated by the regulation of the MAPK and SIRT1 signaling pathways and results in the inhibition of NF-κB transcriptional activity.


Assuntos
Antidepressivos/farmacologia , Depressão/prevenção & controle , Ginsenosídeos/farmacologia , Estresse Psicológico/tratamento farmacológico , Animais , Antidepressivos/administração & dosagem , Comportamento Animal/efeitos dos fármacos , Citocinas/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Ginsenosídeos/administração & dosagem , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Inflamação/tratamento farmacológico , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Neurogênese/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
17.
Psychopharmacology (Berl) ; 237(6): 1783-1793, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32296859

RESUMO

RATIONALE: Patients diagnosed with schizophrenia typically receive life-long treatments with antipsychotic drugs (APDs). However, the impact of chronic APDs treatment on neuroplastic mechanisms in the brain remains largely elusive. OBJECTIVE: Here, we focused on blonanserin, a second-generation antipsychotic (SGA) that acts as an antagonist at dopamine D2, D3, and serotonin 5-HT2A receptors, and represents an important tool for the treatment of schizophrenia. METHODS: We used rats to investigate the ability of chronic treatment blonanserin to modulate the activity of brain structures relevant for schizophrenia, under baseline conditions or in response to an acute forced swim session (FSS). We measured the expression of different immediate early genes (IEGs), including c-Fos, Arc/Arg 3.1, Zif268 and Npas4. RESULTS: Blonanserin per se produced limited changes in the expression of these genes under basal conditions, while, as expected, FSS produced a significant elevation of IEGs transcription in different brain regions. The response of blonanserin-treated rats to FSS show anatomical and gene-selective differences. Indeed, the upregulation of IEGs was greatly reduced in the striatum, a brain structure enriched in dopamine receptors, whereas the upregulation of some genes (Zif268, Npas4) was largely preserved in other regions, such as the prefrontal cortex and the ventral hippocampus. CONCLUSIONS: Taken together, our findings show that chronic exposure to blonanserin modulates selective IEGs with a specific anatomical profile. Moreover, the differential activation of specific brain regions under challenging conditions may contribute to specific clinical features of the drug.


Assuntos
Antipsicóticos/administração & dosagem , Encéfalo/efeitos dos fármacos , Genes Precoces/efeitos dos fármacos , Piperazinas/administração & dosagem , Piperidinas/administração & dosagem , Estresse Psicológico/tratamento farmacológico , Animais , Encéfalo/fisiologia , Esquema de Medicação , Genes Precoces/fisiologia , Masculino , Ratos , Ratos Sprague-Dawley , Receptores Dopaminérgicos/metabolismo , Esquizofrenia/tratamento farmacológico , Esquizofrenia/genética , Estresse Psicológico/genética , Estresse Psicológico/psicologia
18.
Oxid Med Cell Longev ; 2020: 1941480, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32273939

RESUMO

Nonmotor symptoms (NMS) such as anxiety, depression, and cognitive deficits are frequently observed in Parkinson's disease (PD) and precede the onset of motor symptoms by years. We have recently explored the short-term effects of Fluvoxamine, a selective serotonin reuptake inhibitor (SSRI) on dopaminergic neurons in a parkinsonian rat model. Here, we report the long-term effects of Fluvoxamine, on early-life stress-induced changes in the brain and behavior. We specifically evaluated the effects of Fluvoxamine on brain mechanisms that contribute to NMS associated with PD in a unilateral 6-hydroxydopamine-lesioned rat model. A 14-day early postnatal maternal separation protocol was applied to model early-life stress followed by unilateral intracerebral infusion of 6-hydroxydopamine (6-OHDA) to model aspects of parkinsonism in rats. The anxiolytic, antidepressant, and cognitive effects of Fluvoxamine were confirmed using the elevated plus-maze (EPM) test, sucrose preference test (SPT), and Morris water maze (MWM) test. Further to that, our results showed that animals exposed to early-life stress displayed increased plasma corticosterone and malondialdehyde (MDA) levels which were attenuated by Fluvoxamine treatment. A 6-OHDA lesion effect was evidenced by impairment in the limb-use asymmetry test as well as decreased dopamine (DA) and serotonin levels in the striatum, prefrontal cortex, and hippocampus. These effects were surprisingly attenuated by Fluvoxamine treatment in all treated rats. This study is the first to suggest that early and long-term treatment of neuropsychological diseases with Fluvoxamine may decrease the vulnerability of dopaminergic neurons that degenerate in the course of PD.


Assuntos
Fluvoxamina/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Inibidores de Captação de Serotonina/uso terapêutico , Estresse Psicológico/tratamento farmacológico , Animais , Modelos Animais de Doenças , Masculino , Ratos , Ratos Sprague-Dawley , Inibidores de Captação de Serotonina/farmacologia
19.
Biomed Res Int ; 2020: 2794263, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32185198

RESUMO

Background: Fluoxetine (FLU) is the first-line and widely used medication for depression; however, FLU treatment is almost ineffective in 30%-40% of patients with depression. In addition, there are some problems in FLU treatment, such as delayed efficacy, large side effects, and poor tolerance. Chaihu Shugan San (CSS) is a classic and effective antidepressant Chinese herbal medicine that has been used in China for thousands of years. CSS or coadministration of CSS and FLU has become one of the most recommended methods in the treatment of depression in China. However, the specific pathways of CSS and coadministration of CSS and FLU for antidepressant are still unclear. Objective: This study was designed to evaluate the antidepressant effects of CSS and coadministration of CSS and FLU. Methods: The chronic unpredictable mild stress (CUMS) rat model was used to simulate depression. 120 healthy adult male Sprague-Dawley (SD) rats were randomly divided into seven groups: the control group, CUMS group, low-dose CSS group, high-dose CSS group, FLU group, coadministration of low-dose CSS and FLU group, and coadministration of high-dose CSS and FLU group. The rats in different groups were given different interventions. Then, the depression-like behavior and cognitive function were evaluated by the sucrose preference test (SPT), forced swimming test (FST), open field test (OFT), and Y-maze test. What is more, the antidepressant mechanism of CSS and coadministration of CSS and FLU were studied through BDNF mRNA, ERK mRNA, CREB mRNA, BDNF, p-ERK/ERK, and p-CREB/CREB levels in the hippocampus and frontal cortex by Western blot and RT-PCR. Results: Compared with the CUMS group, CSS and coadministration of CSS and FLU could alleviate the depressive symptoms and improve cognitive function in CUMS rats (p < 0.05); CSS and coadministration of CSS and FLU could increase the expression of BDNF, p-CREB/CREB, p-ERK/ERK, and BDNF mRNA, CREB mRNA, and ERK mRNA in the hippocampus and frontal cortex (p < 0.05); CSS and coadministration of CSS and FLU could increase the expression of BDNF, p-CREB/CREB, p-ERK/ERK, and BDNF mRNA, CREB mRNA, and ERK mRNA in the hippocampus and frontal cortex (p < 0.05); CSS and coadministration of CSS and FLU could increase the expression of BDNF, p-CREB/CREB, p-ERK/ERK, and BDNF mRNA, CREB mRNA, and ERK mRNA in the hippocampus and frontal cortex (Discussion and Conclusion. Finally, we found that both CSS and coadministration of CSS and FLU play an antidepressant role, which may be due to the regulation of the BDNF/ERK/CREB signaling pathway in the hippocampus and frontal cortex. Among them, the coadministration of CSS and FLU can enhance the antidepressant effect of CSS or FLU alone, and the underlying mechanism needs further investigation.


Assuntos
Antidepressivos/farmacologia , Fluoxetina/farmacologia , Lobo Frontal/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Nootrópicos/farmacologia , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Comportamento Animal/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Cognição/efeitos dos fármacos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Modelos Animais de Doenças , Lobo Frontal/metabolismo , Hipocampo/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/metabolismo
20.
Pharm. pract. (Granada, Internet) ; 18(1): 0-0, ene.-mar. 2020. tab
Artigo em Inglês | IBECS | ID: ibc-195716

RESUMO

BACKGROUND: Community pharmacists are often the first health professional approached to provide treatment for health issues, including the important mental health challenge, stress. Over-the-counter products for stress almost always are complementary and alternative medicines (CAM) and in Australia no protocol exists for their recommendation and sale in community pharmacies. OBJECTIVE: To assess the quality and relevance of community pharmacists' information gathering (questioning), counselling and product selection when interacting with customers requesting a CAM product for stress and consequently determine whether Australian pharmacy practice indicates the need for guidelines similar to those provided for 'pharmacy only' (S2) and 'pharmacist only' (S3) medicines. METHODS: A covert simulated patient was used to investigate the response of pharmacists to a request for a natural product for stress. The SPs documented the details of the pharmacist-simulated patient interaction immediately on leaving the pharmacy and then re-entered the pharmacy to debrief the pharmacist. The quality of the interaction was scored as a Total CARE (check, assess, respond, explain) Score, based on anticipated questions and counselling advice. The appropriateness of the product was scored as a Product Efficacy Score, based on evidence-based literature. RESULTS: Data from 100 pharmacies was provided. Information gathering illustrated by the questioning components Check and Assess (C and A) of the total CARE score by pharmacists was poor. The number of questions asked ranged from zero (13 pharmacists) to 7 (four pharmacists), the average being 3.1 (SD 1.9). Provision of advice was generally better (a description of the suggested product was offered by 87 pharmacists) but was lacking in other areas (duration of use and side effects were explained by only 41 and 16 pharmacists respectively). The most common product suggested was B-group vitamins (57 pharmacists) followed by a proprietary flower essence product (19 pharmacists). A two-step cluster analysis revealed two sub-groups of pharmacists: one cluster (74 pharmacists) with a high Total CARE score provided an appropriate product. The other cluster (20 pharmacists) had a low total CARE score and provided an inappropriate product. CONCLUSIONS: The pharmacy visits revealed major shortcomings in questioning, counselling and product recommendation. There is a need to develop guidelines for pharmacists to make evidence-based decisions in recommending complementary and alternative medicine


No disponible


Assuntos
Humanos , Serviços Comunitários de Farmácia/organização & administração , Estresse Psicológico/tratamento farmacológico , Medicamentos sem Prescrição/provisão & distribução , Aconselhamento Diretivo/classificação , Austrália/epidemiologia , Terapias Complementares/classificação , Relações Profissional-Paciente
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