RESUMO
Sheng-ma is recorded in the Compendium of Materia Medica and mainly originates from the rhizomes of Cimicifuga dahurica (Turcz.) Maxim. (CD), Cimicifuga heracleifolia Kom. and Cimicifuga foetida L. The alcoholic extract of Cimicifuga foetida L. (Brand name: Ximingting®) has been approved for the treatment of perimenopausal symptoms accompanying hot flash, depression and anxiety in China. However, there's no further study about the antidepressant-like effects of C. dahurica (CD). The aim of this study is to investigate the antidepressant-like effect of CD extracted by 75% ethanol and its possible mechanisms.The neuro-protective effects of CD on injured PC12 cells induced by corticosterone was measured firstly. Then, forced swim test (FST), tail suspension test (TST), reserpine-induced hypothermia, 5-hydroxytryptophan (5-HTP) induced head twitch response in mice and chronic unpredictable mild stress (CUMS) on sucrose preference tests were executed. Moreover, the potential mechanisms were explored by measuring levels of monoamine neurotransmitter in mice frontal cortex and hippocampus, testing monoamine oxidase enzyme A (MAO-A) activities in the brains of CUMS-exposed mice. Results showed that CD (60, 120 mg/kg) can significantly decreased the immobility period in FST and TST in mice without affecting locomotor activity. CD (30 mg/kg, 60 mg/kg, 120 mg/kg) could significantly counteracted reserpine-induced hypothermia and increased the number of head-twitches in 5-HTP induced head twitch response. It was also found that the monoamine neurotransmitter levels in the hippocampus and frontal cortex were significantly increased in 60 mg/kg and 120 mg/kg CD treated mice. In addition, CD (60 and 120 mg/kg) significantly inhibited MAO-A after 6-week CUMS exposure. CD can effectively produce an antidepressant-like effect, which involved with modulation of monoamine regulatory pathways.
Assuntos
Antidepressivos , Cimicifuga , Depressão , Extratos Vegetais , Animais , Antidepressivos/farmacologia , Camundongos , Cimicifuga/química , Células PC12 , Ratos , Extratos Vegetais/farmacologia , Depressão/tratamento farmacológico , Depressão/metabolismo , Modelos Animais de Doenças , Masculino , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/metabolismo , Monoaminas Biogênicas/metabolismo , Reserpina/farmacologia , Camundongos Endogâmicos ICR , Natação/psicologia , Elevação dos Membros Posteriores , Corticosterona/sangue , 5-Hidroxitriptofano/farmacologia , Relação Dose-Resposta a Droga , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/metabolismo , Atividade Motora/efeitos dos fármacos , Preferências Alimentares/efeitos dos fármacosRESUMO
Exposure to chronic and unpredictable stressors can precipitate mood-related disorders in humans, particularly in individuals with pre-existing mental health challenges. L-type calcium channels (LTCCs) have been implicated in numerous neuropsychiatric disorders, as LTCC encoding genes have been identified as candidate risk factors for neuropsychiatric illnesses. In these sets of experiments, we sought to examine the ability of LTCC blockade to alter depression, anxiety, and anhedonic-related behavioral responses to chronic unpredictable stress (CUS) exposure in female and male rats. Rats first underwent either 21 days of CUS or no exposure to chronic stressors, serving as home cage controls (HCC). Then rats were examined for anhedonia-related behavior, anxiety and depression-like behavioral responses as measured by the sucrose preference test (SPT), elevated plus maze (EPM), and forced swim test (FST). CUS exposed females and males showed anhedonic and anxiogenic-like behavioral responses on the SPT and EPM, respectively, when compared to HCCs. In female and male rats, systemic administration of the LTCC blocker isradipine (0.4 mg/kg and 1.2 mg/kg, I.P.) attenuated the CUS-induced decrease in sucrose preference and reversed the CUS-induced decrease in open arm time. In the FST, systemic isradipine decreased immobility time across all groups, consistent with an antidepressant-like response. However, there were no significant differences in forced swim test immobility time between HCC and CUS exposed animals. Taken together, these data point to a role of LTCCs in the regulation of mood disorder-related behavioral phenotype responses to chronic stress exposure.
Assuntos
Anedonia , Ansiedade , Bloqueadores dos Canais de Cálcio , Canais de Cálcio Tipo L , Depressão , Estresse Psicológico , Animais , Anedonia/fisiologia , Anedonia/efeitos dos fármacos , Masculino , Estresse Psicológico/metabolismo , Estresse Psicológico/psicologia , Feminino , Canais de Cálcio Tipo L/metabolismo , Depressão/metabolismo , Ansiedade/metabolismo , Ratos , Bloqueadores dos Canais de Cálcio/farmacologia , Ratos Sprague-Dawley , Modelos Animais de Doenças , Fenótipo , Preferências Alimentares/efeitos dos fármacos , Preferências Alimentares/fisiologiaRESUMO
The etiology of major depressive disorder (MDD) remains poorly understood. Our previous studies suggest a role for the aryl hydrocarbon receptor (AhR) in depression. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a toxic environmental contaminant, with a high AhR binding affinity, and an established benchmark for assessing AhR activity. Therefore, this study examined the effect of TCDD on depression-like behaviors. Female mice were fed standard chow or a high-fat diet (HFD) for 11 weeks, and their weight was recorded. Subsequently, they were tested for baseline sucrose preference and splash test grooming. Then, TCDD (0.1⯵g/kg/day) or vehicle was administered orally for 28 days, and mice were examined for their sucrose preference and performances in the splash test, forced swim test (FST), and Morris water maze (MWM) task. TCDD significantly decreased sucrose preference, increased FST immobility time, and decreased groom time in chow-fed mice. HFD itself significantly reduced sucrose preference. However, TCDD significantly increased FST immobility time and decreased groom time in HFD-fed mice. A small decrease in bodyweight was observed only at the fourth week of daily TCDD administration in chow-fed mice, and no significant effects of TCDD on bodyweights were observed in HFD-fed mice. TCDD did not have a significant effect on spatial learning in the MWM. Thus, this study demonstrated that TCDD induces a depression-like state, and the effects were not due to gross lethal toxicity. This study further suggests that more studies should examine a possible role for AhR and AhR-active environmental pollutants in precipitating or worsening MDD.
Assuntos
Depressão , Dibenzodioxinas Policloradas , Animais , Dibenzodioxinas Policloradas/toxicidade , Feminino , Depressão/induzido quimicamente , Depressão/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Aprendizagem em Labirinto/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Natação/psicologia , Receptores de Hidrocarboneto Arílico/metabolismo , Preferências Alimentares/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Fenótipo , Asseio Animal/efeitos dos fármacosRESUMO
INTRODUCTION: High sugar intake is associated with many chronic diseases. However, non-caloric sweeteners (NCSs) might fail to successfully replace sucrose due to the mismatch between their rewarding sweet taste and lack of caloric content. The natural NCS erythritol has been proposed as a sugar substitute due to its satiating properties despite being non-caloric. We aimed to compare brain responses to erythritol vs. sucrose and the artificial NCS sucralose in a priori taste, homeostatic, and reward brain regions of interest (ROIs). METHODS: We performed a within-subject, single-blind, counterbalanced fMRI study in 30 healthy men (mean ± SEM age:24.3 ± 0.8 years, BMI:22.3 ± 0.3 kg/m2). Before scanning, we individually matched the concentrations of both NCSs to the perceived sweetness intensity of a 10% sucrose solution. During scanning, participants received 1 mL sips of the individually titrated equisweet solutions of sucrose, erythritol, and sucralose, as well as water. After each sip, they rated subjective sweetness liking. RESULTS: Liking ratings were significantly higher for sucrose and sucralose vs. erythritol (both pHolm = 0.0037); water ratings were neutral. General Linear Model (GLM) analyses of brain blood oxygen level-depended (BOLD) responses at qFDR<0.05 showed no differences between any of the sweeteners in a priori ROIs, but distinct differences were found between the individual sweeteners and water. These results were confirmed by Bayesian GLM and machine learning-based models. However, several brain response patterns mediating the differences in liking ratings between the sweeteners were found in whole-brain multivariate mediation analyses. Both subjective and neural responses showed large inter-subject variability. CONCLUSION: We found lower liking ratings in response to oral administration of erythritol vs. sucrose and sucralose, but no differences in neural responses between any of the sweeteners in a priori ROIs. However, differences in liking ratings between erythritol vs. sucrose or sucralose are mediated by multiple whole-brain response patterns.
Assuntos
Encéfalo , Eritritol , Preferências Alimentares , Imageamento por Ressonância Magnética , Sacarose , Edulcorantes , Humanos , Eritritol/farmacologia , Eritritol/análogos & derivados , Eritritol/administração & dosagem , Masculino , Adulto Jovem , Adulto , Sacarose/análogos & derivados , Sacarose/administração & dosagem , Sacarose/farmacologia , Preferências Alimentares/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/fisiologia , Método Simples-Cego , Edulcorantes/administração & dosagem , Edulcorantes/farmacologia , Paladar/efeitos dos fármacos , Administração Oral , Percepção Gustatória/efeitos dos fármacos , RecompensaRESUMO
In addition to its sweet taste, glucose has potent and rapid postoral actions (appetition) that enhance its reward value. This has been demonstrated by the experience-induced preference for glucose over initially preferred nonnutritive sweetener solutions in 24-h choice tests. However, some sweetener solutions (e.g., 0.8% sucralose) have inhibitory postoral actions that may exaggerate glucose appetition whereas others (e.g., 0.1% sucralose + 0.1% saccharin, S+S) do not. Experiment 1 revealed that food-restricted (FR) male C57BL/6J mice displayed similar rapid glucose appetition effects (stimulation of glucose licking within minutes) and conditioned flavor preferences following 1-h experience with flavored 0.8% sucralose or 0.1% S+S and 8% glucose solutions. Thus, the inhibitory effects of 0.8% sucralose observed in 24-h tests were not apparent in 1-h tests. Experiment 2 evaluated the effects of food deprivation state and sweetener concentration on glucose appetition in female mice. Unlike FR mice tested with 0.1% S+S and 8% glucose, ad libitum (AL) fed mice displayed no stimulation of 8% glucose licking in the 1-h tests. A second ad libitum group (AL) tested with 0.2% S+S and 16% glucose solutions displayed stimulation of 16% glucose licking by the third 1-h test. Both AL groups, like the FR group, developed a preference for the glucose-paired flavor over the S+S paired flavor. Thus, food restriction promotes increased glucose licking but is not required for a conditioned preference. The FR male mice (Exp. 1) and FR female mice (Exp. 2) showed similar appetition responses (licking stimulation and flavor preference) to 8% glucose.
Assuntos
Privação de Alimentos , Glucose , Camundongos Endogâmicos C57BL , Caracteres Sexuais , Sacarose , Edulcorantes , Animais , Masculino , Feminino , Camundongos , Glucose/farmacologia , Privação de Alimentos/fisiologia , Edulcorantes/farmacologia , Edulcorantes/administração & dosagem , Sacarose/farmacologia , Sacarose/administração & dosagem , Sacarose/análogos & derivados , Preferências Alimentares/efeitos dos fármacos , Preferências Alimentares/fisiologia , Sacarina/farmacologia , Sacarina/administração & dosagem , Relação Dose-Resposta a DrogaRESUMO
The high prevalence of obesity has become a pressing global public health problem and there exists a strong association between increased BMI and mortality at a BMI of 25 kg/m2 or higher. The prevalence of obesity is higher among middle-aged adults than among younger groups and the combination of aging and obesity exacerbate systemic inflammation. Increased inflammatory cytokines such as interleukin 6 and tumor necrosis factor alpha (TNFα) are hallmarks of obesity, and promote the secretion of hepatic C-reactive protein (CRP) which further induces systematic inflammation. The neuropeptide oxytocin has been shown to have anti-obesity and anti-inflammation effects, and also suppress sweet-tasting carbohydrate consumption in mammals. Previously, we have shown that the Japanese herbal medicine Kamikihito (KKT), which is used to treat neuropsychological stress disorders in Japan, functions as an oxytocin receptors agonist. In the present study, we further investigated the effect of KKT on body weight (BW), food intake, inflammation, and sweet preferences in middle-aged obese mice. KKT oral administration for 12 days decreased the expression of pro-inflammatory cytokines in the liver, and the plasma CRP and TNFα levels in obese mice. The effect of KKT administration was found to be different between male and female mice. In the absence of sucrose, KKT administration decreased food intake only in male mice. However, while having access to a 30% sucrose solution, both BW and food intake was decreased by KKT administration in male and female mice; but sucrose intake was decreased in female mice alone. In addition, KKT administration decreased sucrose intake in oxytocin deficient lean mice, but not in the WT lean mice. The present study demonstrates that KKT ameliorates chronic inflammation, which is strongly associated with aging and obesity, and decreases food intake in male mice as well as sucrose intake in female mice; in an oxytocin receptor dependent manner.
Assuntos
Dieta Hiperlipídica , Medicamentos de Ervas Chinesas , Inflamação , Camundongos Endogâmicos C57BL , Obesidade , Animais , Obesidade/metabolismo , Obesidade/tratamento farmacológico , Masculino , Camundongos , Dieta Hiperlipídica/efeitos adversos , Inflamação/metabolismo , Feminino , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Sacarose/administração & dosagem , Preferências Alimentares/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Ocitocina/farmacologia , Medicina Kampo , População do Leste AsiáticoRESUMO
Although the brain can discriminate between various sweet substances, the underlying neural mechanisms of this complex behavior remain elusive. This study examines the role of the anterior paraventricular nucleus of the thalamus (aPVT) in governing sweet preference in mice. We fed the mice six different diets with equal sweetness for six weeks: control diet (CD), high sucrose diet (HSD), high stevioside diet (HSSD), high xylitol diet (HXD), high glycyrrhizin diet (HGD), and high mogroside diet (HMD). The mice exhibited a marked preference specifically for the HSD and HSSD. Following consumption of these diets, c-Fos expression levels in the aPVT were significantly higher in these two groups compared to the others. Utilizing fiber photometry calcium imaging, we observed rapid activation of aPVT neurons in response to sucrose and stevioside intake, but not to xylitol or water. Our findings suggest that aPVT activity aligns with sweet preference in mice, and notably, stevioside is the sole plant-based sweetener that elicits an aPVT response comparable to that of sucrose.
Assuntos
Neurônios , Edulcorantes , Animais , Edulcorantes/administração & dosagem , Edulcorantes/farmacologia , Masculino , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-fos/metabolismo , Preferências Alimentares/fisiologia , Preferências Alimentares/efeitos dos fármacosRESUMO
Objectives: Inbred mouse strains differ in the pharmacology mediating sugar and fat intake and conditioned flavor preferences (CFP). C57BL/6, BALB/c and SWR inbred mice are differentially sensitive to dopamine (DA) D1, opioid and muscarinic receptor antagonism of sucrose, saccharin or fat intake, and to DA, opioid, muscarinic and N-methyl-D-aspartate (NMDA) receptor antagonism of acquisition of sucrose-CFP. DA D1, opioid and NMDA receptor antagonists differentially alter fat (Intralipid)-CFP in BALB/c and SWR mice. The present study examined whether naltrexone, SCH23390 or MK-801 altered acquisition and expression of Intralipid-CFP in C57BL/6 mice.Methods: In acquisition, groups of male food-restricted C57BL/6 mice received vehicle, naltrexone (1, 5 mg/kg), SCH23390 (50, 200 nmol/kg) or MK-801 (100, 200 µg/kg) before 10 training sessions in which mice alternately consumed two novel-flavored 5% (CS+) and 0.5% (CS-) Intralipid solutions. Six two-bottle CS choice tests followed with both flavors mixed in 0.5% Intralipid without injections. In expression, C57BL/6 mice underwent the 10 training sessions without injections followed by two-bottle CS choice tests 30 min following vehicle, naltrexone (1, 5 mg/kg), SCH23390 (200, 800 nmol/kg) or MK-801 (100, 200 µg/kg).Results: Fat-CFP acquisition in C57BL/6 mice was significantly though marginally reduced following naltrexone, SCH23390 and MK-801. Fat-CFP expression was similarly reduced by naltrexone, SCH23390 and MK-801 in C57BL/6 mice. Discussion: C57BL/6 mice were more sensitive to DA D1, opioid and NMDA antagonists in the expression of fat-CFP relative to sugar-CFP, but were less sensitive to DA D1 and NMDA antagonists in the acquisition of fat-CFP relative to sugar-CFP.
Assuntos
Gorduras na Dieta , Antagonistas de Entorpecentes/farmacologia , Receptores de Dopamina D1/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Paladar/fisiologia , Animais , Benzazepinas/farmacologia , Condicionamento Clássico , Maleato de Dizocilpina/farmacologia , Emulsões , Preferências Alimentares/efeitos dos fármacos , Preferências Alimentares/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Naltrexona/farmacologia , Fosfolipídeos , Receptores Opioides , Óleo de Soja , Paladar/efeitos dos fármacosRESUMO
In addition to the taste receptors corresponding to the six basic taste qualities-sweet, salty, sour, bitter, umami, and fatty-another type of taste receptor, calcium-sensing receptor (CaSR), is found in taste-bud cells. CaSR is called the 'kokumi' receptor because its agonists increase sweet, salty and umami tastes to induce 'koku', a Japanese word meaning the enhancement of flavor characters such as thickness, mouthfulness, and continuity. Koku is an important factor for enhancing food palatability. However, it is not well known whether other kokumi-receptors and substances exist. Here, we show that ornithine (L-ornithine but not D-ornithine) at low concentrations that do not elicit a taste of its own, enhances preferences to sweet, salty, umami, and fat taste solutions in mice. Increased preference to monosodium glutamate (MSG) was the most dominant effect. Antagonists of G-protein-coupled receptor family C group 6 subtype A (GPRC6A) abolished the additive effect of ornithine on MSG solutions. The additive effects of ornithine on taste stimuli are thought to occur in the oral cavity, and are not considered post-oral events because ornithine's effects were confirmed in a brief-exposure test. Moreover, the additive effects of ornithine and the action of the antagonist were verified in electrophysiological taste nerve responses. Immunohistochemical analysis implied that GPRC6A was expressed in subsets of type II and type III taste cells of mouse circumvallate papillae. These results are in good agreement with those reported for taste modulation involving CaSR and its agonists. The present study suggests that ornithine is a kokumi substance and GPRC6A is a newly identified kokumi receptor.
Assuntos
Preferências Alimentares/efeitos dos fármacos , Ornitina/farmacologia , Paladar/fisiologia , Animais , Nervo da Corda do Tímpano/efeitos dos fármacos , Nervo da Corda do Tímpano/fisiologia , Masculino , Camundongos Endogâmicos C57BL , Estimulação Física , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Receptores Acoplados a Proteínas G/metabolismo , Soluções , Paladar/efeitos dos fármacos , Papilas Gustativas/efeitos dos fármacos , Papilas Gustativas/fisiologiaRESUMO
Stress during pregnancy is not only detrimental to a woman's own physical and mental health, but can also cause changes in the intrauterine environment and even have an impact on later growth and development, this study was designed to understand the changes of gut microbiota in the maternal and offspring caused by prenatal chronic stress, and to explore the regulatory effect of LBP on gut microbiota, and then to improve the emotional damage caused by prenatal chronic stress in the offspring. A rat model of prenatal chronic stress was made and used LBP to intervene by gavage. Fresh feces of offspring were collected, the concentration of microbial metabolites were tested by ELISA. Illumina MiSeqPE300 sequencing technology was used to determine the sequence of 16S rRNA V3-V4 of microorganisms. On the PND 42, the emotional function of offspring were tested by open-field test (OFT), sucrose preference test (SPT) and tail of suspend test (TST). Results indicated that stress factors increased the plasma corticosterone level of rats during pregnancy and they appeared depressive behaviors. The body weight of offspring during prenatal chronic stress was lower than the control group, and the plasma corticosterone level was increased. Prenatal chronic stress had a significant impact on emotional performance of the offspring on OFT, SPT and TST. Alpha diversity of gut microbiota and microbiota composition in offspring of prenatal chronic stress was attenuated and some relationships existed between these parameters. LBP treatment reduced offspring's plasma corticosterone level and improved their body weight, changed the emotional function, increased the diversity of gut microbiota. Collectively, these findings disclose that prenatal chronic stress not only causes emotional injury on the offspring, but also changes the gut microbiota of the mother and offspring; LBP may regulate the intestinal flora of the mother, then reducing the influence of stress factors on the emotional injury of offspring.
Assuntos
Bactérias/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Emoções/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal , Estresse Psicológico/tratamento farmacológico , Sintomas Afetivos/etiologia , Sintomas Afetivos/microbiologia , Sintomas Afetivos/prevenção & controle , Sintomas Afetivos/psicologia , Animais , Bactérias/crescimento & desenvolvimento , Eixo Encéfalo-Intestino/efeitos dos fármacos , Doença Crônica , Modelos Animais de Doenças , Disbiose , Feminino , Preferências Alimentares/efeitos dos fármacos , Masculino , Teste de Campo Aberto/efeitos dos fármacos , Gravidez , Ratos Sprague-Dawley , Estresse Psicológico/complicações , Estresse Psicológico/microbiologia , Estresse Psicológico/psicologiaRESUMO
Although dopamine plays a prominent role in mediating cocaine's abuse-related effects, the specific roles of dopamine receptor subtypes are not fully understood. Whereas the effects of drugs acting at dopamine D2-like receptors (D2Rs) have been characterized, less is known about dopamine D1-like receptors (D1Rs). The present experiments examined the effects of drugs with varying intrinsic efficacy at D1R on the relative reinforcing strength of cocaine in male cynomolgus monkeys. Use of socially housed monkeys permitted the assessment of whether social status influenced the behavioral effects of D1R-acting drugs. The high-efficacy D1R agonist SKF 81297, low-efficacy D1R agonist SKF 38393, and D1R antagonist SCH 23390 were administered acutely to monkeys self-administering cocaine under a food-cocaine choice procedure in which a cocaine-choice dose-effect curve was determined daily. To assess selectivity of behavioral effects on cocaine choice, effects of doses that did not disrupt responding (indicated by a ≥35% decrease in total reinforcers delivered) were analyzed. Neither SKF 81297 nor SCH 23390 affected cocaine choice in dominant or subordinate monkeys. However, the low-efficacy agonist SKF 38393 selectively decreased cocaine choice; this effect was larger and only reached statistical significance in subordinate monkeys. Increasing the time between D1-acting drug administration and the cocaine choice session did not affect these results. The results indicate that, like D2R-acting drugs, the behavioral effects of D1R-acting drugs on cocaine choice can vary according to intrinsic efficacy and social status. Moreover, they demonstrate that D1R-acting drugs affect behavior under a narrower range of conditions than D2R-acting drugs. SIGNIFICANCE STATEMENT: Cocaine use disorder represents an insidious public health concern with no Food and Drug Administration-approved medications. Although dopamine receptors have been strongly implicated in mediating the abuse-related effects of cocaine, the roles of dopamine receptor subtypes are incompletely understood. The present study in nonhuman primates found that cocaine choice was decreased only by a low-efficacy D1R agonist, and that this effect depended on the social status of the monkey.
Assuntos
Comportamento de Escolha/efeitos dos fármacos , Cocaína/administração & dosagem , Agonistas de Dopamina/farmacologia , Preferências Alimentares/efeitos dos fármacos , Receptores de Dopamina D1/agonistas , Interação Social/efeitos dos fármacos , 2,3,4,5-Tetra-Hidro-7,8-Di-Hidroxi-1-Fenil-1H-3-Benzazepina/farmacologia , Animais , Comportamento de Escolha/fisiologia , Condicionamento Operante/efeitos dos fármacos , Condicionamento Operante/fisiologia , Relação Dose-Resposta a Droga , Preferências Alimentares/fisiologia , Preferências Alimentares/psicologia , Ligantes , Macaca fascicularis , Masculino , Receptores de Dopamina D1/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Xiaoyaosan (XYS), a representative and classic prescription in traditional Chinese medicines (TCMs), has been used for thousands of years for treating depression. The anti-depression effect of XYS has been demonstrated both clinically and experimentally. However, it is still unclear that whether XYS could regulate the abnormalities of gut microbiota and metabolites of cecum induced by depression, and in which way. This study aimed to explore the underlying mechanism of the anti-depressant effects of XYS from the perspective of cecal microbiota and metabolites. MATERIALS AND METHODS: Chronic unpredictable mild stress (CUMS)-induced depression-like rats were used as the depression animal model. Various classic behavioral tests were performed to assess the anti-depressant effects of XYS. Additionally, the composition, the richness, and the diversity of the cecum microbiota were assessed by 16S rRNA gene sequencing technology. Besides, the metabolic profiling of cecum samples was analyzed by 1H-NMR metabolomics. Multivariate data analysis was then applied to screen the differential metabolites and to characterize the changes in cecum metabolites. Moreover, a correlation analysis between differential metabolites and crucial microbiota was conducted. RESULTS: XYS significantly improved depressive behaviors and the abnormal diversity of cecum microbiota induced by CUMS. At the phylum level, XYS could significantly increase the abundance of Firmicutes while decrease the abundance of Actinobacteria in depressed rats. XYS significantly regulated the abundances of 9 out of 13 potential microbial biomarkers at the genus level. Cecal metabolomics showed that XYS could also regulate the abnormal levels of alanine, proline, lactate, and valine of depression rats. CONCLUSIONS: This study revealed, for the first time, from the perspectives of microbiota and cecum metabolites, the anti-depression mechanisms of XYS. This study is of significance for not only comprehensively understanding the anti-depression effects and mechanisms of XYS, but also for providing a research approach for revealing the underlying mechanisms of action of TCMs, i.e. to apply a combination of 16S rRNA gene sequencing and metabolomics.
Assuntos
Antidepressivos/farmacologia , Ceco/microbiologia , Depressão/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Metaboloma/efeitos dos fármacos , Microbiota/efeitos dos fármacos , Aminoácidos/metabolismo , Animais , Antidepressivos/uso terapêutico , Comportamento Animal/efeitos dos fármacos , Biomarcadores/metabolismo , Peso Corporal/efeitos dos fármacos , Depressão/etiologia , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/uso terapêutico , Preferências Alimentares/efeitos dos fármacos , Masculino , Medicina Tradicional Chinesa , Microbiota/genética , Atividade Motora/efeitos dos fármacos , Análise de Componente Principal , Ratos Sprague-Dawley , Estresse Psicológico/complicações , Estresse Psicológico/microbiologiaRESUMO
ALTERTASTE is a prospective study to evaluate changes in taste/flavor perception and food preferences in patients treated with adjuvant or neoadjuvant chemotherapy for breast or colorectal cancer. The study adopts a longitudinal approach. Taste and odor responsiveness, food preferences and habits, emotions elicited by foods, and quality of life will be measured at six-time points: before chemotherapy (T0), after two cycles (T1, after around 1 month), after four cycles (T2, after around 2 months), after six cycles (T3, after around 4 months), at the end of chemotherapy (T4, after around 6 months) and 3 months after the conclusion of the therapy (T5). In addition, patients will be characterized for oral responsiveness and their psychological traits and attitudes toward food. The ALTERTASTE trial is expected to improve the understanding of the impact of chemotherapy on taste and smell and the repercussions of these alterations on food behaviors. Furthermore, the trial aims to develop an easy and reliable procedure to test smell, taste and food behavior alterations to allow a routine measure with patients. Clinical trial registration: NCT04495387 (ClinicalTrials.gov).
Lay abstract Malnutrition (under- or over-nutrition) is highly prevalent in cancer patients receiving chemotherapy and is an important predictor of morbidity, mortality, treatment response and toxicity. Alterations in taste and smell are frequently reported as side effects of chemotherapy and may contribute strongly to malnutrition through an impact on eating behaviors and to a worse quality of life. ALTERTASTE is a prospective longitudinal study to evaluate changes in taste/flavor perception and food preferences in patients treated with chemotherapy for breast, colon or rectal cancer. Taste and odor responsiveness, food preferences and habits, emotions elicited by foods, and quality of life will be measured at six-time points: before chemotherapy (T0), after two cycles (T1, after around 1 month), after four cycles (T2, after around 2 months), after six cycles (T3, after around 4 months), at the end of chemotherapy (T4, after around 6 months) and 3 months after the conclusion of the therapy (T5). In addition, patients will be characterized for oral responsiveness and psychological traits and attitudes toward food. The ALTERTASTE trial is expected to improve the understanding of the impact of chemotherapy on taste and smell and the repercussions of these alterations on food behaviors.
Assuntos
Antineoplásicos/administração & dosagem , Preferências Alimentares/efeitos dos fármacos , Desnutrição/prevenção & controle , Neoplasias/tratamento farmacológico , Qualidade de Vida , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Preferências Alimentares/psicologia , Humanos , Estudos Longitudinais , Masculino , Desnutrição/etiologia , Desnutrição/psicologia , Pessoa de Meia-Idade , Neoplasias/complicações , Estudos Observacionais como Assunto , Estudos Prospectivos , Olfato/efeitos dos fármacos , Paladar/efeitos dos fármacos , Resultado do Tratamento , Adulto JovemRESUMO
Amelioration of oxidative stress via promoting the endogenous antioxidant system and enhancement of monoamines in brain were the important underlying antidepressant mechanism of protocatechuic acid (PCA). The aim of the present study is to explore the potential antidepressant mechanism(s) PCA in chronic unpredictable mild stress (CUMS) mice. Mice were subjected to CUMS protocol for 4 weeks, and administered with PCA (100 and 200 mg/kg) and fluoxetine (20 mg/kg) for 24 days (from day 8th to 31st). Behavioral (sucrose preference, immobility time, exploratory behavior), and biochemical alterations such as serum corticosterone, brain derived neurotrophic factor (BDNF), inflammatory cytokines, tumor necrosis factor- α (TNF-α), interleukin-6 (IL-6), and antioxidants parameters were investigated. Experimental findings revealed that CUMS subjected mice exhibited significant impairment in behavioral alterations, such as increased immobility time, impaired preference to the sucrose solution, BDNF levels and, serum corticosterone, cytokines, malondialdehyde (MDA) formation with impaired antioxidants in the hippocampus and cerebral cortex. Administration of PCA to CUMS mice attenuated the immobility time, serum corticosterone, cytokines TNF-α, and IL-6, MDA formation and improved sucrose preference, including restoration of BDNF level. Thus, the present findings demonstrated the antidepressant potential of PCA which is largely achieved probably through maintaining BDNF level, and by modulation of the oxidative stress response, cytokines systems, and antioxidant defense system in mice.
Assuntos
Antidepressivos/farmacologia , Antioxidantes/farmacologia , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Hidroxibenzoatos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Psicológico/tratamento farmacológico , Animais , Biomarcadores/sangue , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Fator Neurotrófico Derivado do Encéfalo/sangue , Doença Crônica , Modelos Animais de Doenças , Comportamento Exploratório/efeitos dos fármacos , Preferências Alimentares/efeitos dos fármacos , Interleucina-6/sangue , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Estresse Psicológico/sangue , Estresse Psicológico/fisiopatologia , Estresse Psicológico/psicologia , Fator de Necrose Tumoral alfa/sangueRESUMO
BACKGROUND: A low-protein diet can induce compensatory intake of excess energy. This must be better evaluated to anticipate the obesogenic risk that may result from the dietary recommendations for reducing animal protein consumption. OBJECTIVES: We aimed to further characterize the behavioral and physiological responses to a reduction in dietary protein and to identify the determinants of protein appetite. METHODS: Thirty-two male Wistar rats [4 wk old, (mean ± SEM) 135 ± 32 g body weight] were fed a low-protein (LP; 6% energy value) or normal-protein (NP; 20%) diet for 8 wk. Food intake and body mass were measured during the entire intervention. During self-selection sessions after 4 wk of experimental diets, we evaluated rat food preference between LP, NP, or high-protein (HP; 55%) pellets. At the end of the experiment, we assessed their hedonic response [ultrasonic vocalizations (USVs)] and c-Fos neuronal activation in the olfactory tubercle and nucleus accumbens (NAcc) associated with an LP or HP meal. RESULTS: Rats fed an LP diet had greater food intake (24%), body weight (5%), and visceral adiposity (30%) than NP rats. All LP rats and half of the NP rats showed a nearly exclusive preference for HP pellets during self-selection sessions, whereas the other half of the NP rats showed no preference. This suggests that the appetite for proteins is driven not only by a low protein status but also by individual traits in NP rats. LP or HP meal induced similar USV emission and similar neuronal activation in the NAcc in feed-deprived LP and NP rats, showing no specific response linked to protein appetite. CONCLUSIONS: Protein appetite in rats is driven by low protein status or individual preferences in rats receiving adequate protein amounts. This must be considered and further analyzed, in the context of current recommendations for protein intake reduction.
Assuntos
Apetite/efeitos dos fármacos , Dieta com Restrição de Proteínas , Proteínas Alimentares/farmacologia , Ingestão de Alimentos/efeitos dos fármacos , Ingestão de Energia/efeitos dos fármacos , Preferências Alimentares/efeitos dos fármacos , Fenótipo , Adiposidade , Animais , Peso Corporal , Proteínas Alimentares/administração & dosagem , Gordura Intra-Abdominal , Masculino , Carne , Núcleo Accumbens , Obesidade , Tubérculo Olfatório , Ratos WistarRESUMO
Cannabinoids have an important role in regulating feeding behaviors via cannabinoid receptors in mammals. Cannabinoids also exhibit potential therapeutic functions in Drosophila melanogaster, or fruit fly that lacks cannabinoid receptors. However, it remains unclear whether cannabinoids affect food consumption and metabolism in a cannabinoid receptors-independent manner in flies. In this study, we systematically investigated pharmacological functions of various cannabinoids in modulating food preference and consumption in flies. We show that flies display preferences for consuming cannabinoids, independent of two important sensory regulators Poxn and Orco. Interestingly, phyto- and endo- cannabinoids exhibit an inhibitory effect on food intake. Unexpectedly, the non-selective CB1 receptor antagonist AM251 attenuates the suppression of food intake by endocannabinoids. Moreover, the endocannabinoid anandamide (AEA) and its metabolite inhibit food intake and promote resistance to starvation, possibly through reduced lipid metabolism. Thus, this study has provided insights into a pharmacological role of cannabinoids in feeding behaviors using an adult Drosophila model.
Assuntos
Canabinoides/farmacologia , Drosophila melanogaster/efeitos dos fármacos , Preferências Alimentares/efeitos dos fármacos , Animais , Ácidos Araquidônicos/farmacologia , Agonistas de Receptores de Canabinoides/farmacologia , Drosophila melanogaster/fisiologia , Ingestão de Alimentos/efeitos dos fármacos , Endocanabinoides/farmacologia , Masculino , Alcamidas Poli-Insaturadas/farmacologia , Receptor CB1 de Canabinoide/agonistas , Receptor CB1 de Canabinoide/antagonistas & inibidores , Receptor CB1 de Canabinoide/metabolismoRESUMO
RATIONALE: Past research suggests that people with opioid dependence show increased consumption of sweet food, but it is unclear if this is influenced by altered taste preference and/or taste perception. OBJECTIVES: We tested whether people prescribed opioid substitution therapy (OST) exhibited a shift in preference towards sweeter flavours, and altered perception of sweetness, and explored whether these measures of taste preference/perception were associated with measures of opioid use. METHODS: Three groups of participants (people prescribed OST, n=36; people with past opioid dependence, but now abstinent from all opioids, n=18; and controls with no history of substance dependence other than nicotine, n=29) provided ratings of "sweetness", "liking", and "desire" of 4 solutions with varying concentrations of sucrose. RESULTS: We did not find significant differences between groups in the effect of sucrose concentration on "sweetness", "liking", or "desire" ratings. However, among those prescribed OST, frequency of recent illicit opioid use was associated with reduced perception of "sweetness" of low sucrose concentrations. Higher methadone dose was associated with a shift towards liking sweeter concentrations. Among those with past opioid dependence, longer duration of abstinence from opioids was associated with a shift towards liking sweeter concentrations. CONCLUSIONS: Among people currently dependent on opioids, reduced sensitivity to low levels of sweetness and increased preference for sweeter flavours may be associated with increased dependence on opioids. Among those who have ceased opioid use, the association between preference for sweeter flavours and duration of abstinence is a novel finding that deserves further investigation.
Assuntos
Disgeusia/epidemiologia , Preferências Alimentares/efeitos dos fármacos , Transtornos Relacionados ao Uso de Opioides/complicações , Paladar/efeitos dos fármacos , Adolescente , Adulto , Feminino , Humanos , Masculino , Metadona/uso terapêutico , Pessoa de Meia-Idade , Tratamento de Substituição de Opiáceos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Sacarose/farmacologia , Percepção Gustatória , Adulto JovemRESUMO
BACKGROUND: Preclinical studies into drug vs. nondrug choice have emerged to better model and investigate the neurobehavioral mechanisms underlying drug preference. Current literature has suggested that drugs of abuse have inherently low value, thus promoting food preference. Herein, we examined remifentanil vs. food choice to test both the relative value hypothesis and the 'direct effects' (pharmacological effects of drugs on alternative reinforcers) hypothesis of opioid preference. METHODS: Adult male rats were trained under two choice procedures (controlled vs. uncontrolled reinforcer frequency) for remifentanil vs. food choice. Furthermore, a series of procedural manipulations known to affect drug reinforcement were tested under both choice procedures. Using remifentanil self-administration data, pharmacokinetic profiles were calculated and analyzed to determine if opioid intake was related to opioid preference. RESULTS: Both choice procedures produced dose-dependent preference. Moreover, procedural manipulations produced comparable changes in remifentanil preference under both choice procedures. In addition, calculated pharmacokinetic data revealed that preference was dissociable from intake under the controlled reinforcer frequency choice procedure. CONCLUSIONS: When compared to the 'direct effects' hypothesis, remifentanil preference was better predicted by the relative value hypothesis, formalized in generalized matching. Use of a controlled reinforcer frequency schedule successfully removed the drug preference-intake confound found in most drug-choice procedures. Importantly, drug preference under the controlled reinforcer frequency schedule remained sensitive to procedural manipulations known to affect drug reinforcement. Thus, given that differential drug intake itself affects neurobiological measurements, future use of controlled reinforcer frequency schedules may help to better isolate the neurobehavioral mechanisms that mediate opioid preference.
Assuntos
Analgésicos Opioides/farmacologia , Preferências Alimentares/efeitos dos fármacos , Remifentanil/farmacologia , Analgésicos Opioides/administração & dosagem , Animais , Comportamento de Escolha/efeitos dos fármacos , Condicionamento Operante/efeitos dos fármacos , Relação Dose-Resposta a Droga , Masculino , Ratos , Esquema de Reforço , Reforço Psicológico , AutoadministraçãoRESUMO
Food neophobia is a behavior observed in rodents involving reduced consumption of a novel food or drink. In the absence of negative post-ingestive consequences, consumption increases with exposure (attenuation of neophobia), which is seen as an associative safe memory. Olfaction and gustation are sensory modalities essential for the development of a food preference. However, little is known about the neural mechanisms underlying neophobia to a food-related odor stimulus. In the present study, we examined the effect of pharmacological inactivation of the ventral hippocampus (vHPC) on neophobia to orally consumed solutions in rats using muscimol, a gamma aminobutyric acid type A receptor agonist. Two different types of solutions, almond odor (benzaldehyde) and sweet taste (saccharin), were prepared. In the results, microinjections of muscimol into the bilateral vHPC before the first odor and taste exposures did not alter the neophobic reactions of the rats to each stimulus. However, in the second odor, but not taste, exposure, the muscimol-injected rats showed higher consumption in comparison to that observed in the control rats, suggesting that the vHPC inactivation facilitates the attenuation of odor neophobia. On the other hand, intra-vHPC muscimol microinjections after the first odor and taste exposures did not facilitate consumption at the second exposures. These results indicate that neural activations within vHPC during orally consuming a novel odor, but not taste, solution play an inhibitory role in the subsequent attenuation of neophobia.
Assuntos
Comportamento Animal/fisiologia , Preferências Alimentares/fisiologia , Agonistas de Receptores de GABA-A/farmacologia , Hipocampo/efeitos dos fármacos , Muscimol/farmacologia , Percepção Olfatória/fisiologia , Percepção Gustatória/fisiologia , Animais , Comportamento Animal/efeitos dos fármacos , Preferências Alimentares/efeitos dos fármacos , Agonistas de Receptores de GABA-A/administração & dosagem , Masculino , Muscimol/administração & dosagem , Percepção Olfatória/efeitos dos fármacos , Ratos , Ratos Wistar , Percepção Gustatória/efeitos dos fármacosRESUMO
Phosphodiesterase 2 is one of the phosphodiesterase (PDEs) family members that regulate cyclic nucleotide (namely cAMP and cGMP) concentrations. The present study determined whether PDE2 inhibition could rescue post-traumatic stress disorder (PTSD)-like symptoms. Mice were subjected to single prolonged stress (SPS) and treated with selective PDE2 inhibitor Bay 60-7550 (0.3, 1, or 3 mg/kg, i.p.). The behavioral tests such as forced swimming, sucrose preference test, open field, elevated plus maze, and contextual fear paradigm were conducted to determine the effects of Bay 60-7550 on SPS-induced depression- and anxiety-like behavior and fear memory deficits. The results suggested that Bay 60-7550 reversed SPS-induced depression- and anxiety-like behavior and fear memory deficits. Moreover, Bay 60-7550 prevented SPS-induced changes in the adrenal gland index, synaptic proteins synaptophysin and PSD95 expression, PKA, PKG, pCREB, and BDNF levels in the hippocampus and amygdala. These effects were completely prevented by PKG inhibitor KT5823. While PKA inhibitor H89 also prevented Bay 60-7550-induced pCREB and BDNF expression, but only partially prevented the effects on PSD95 expression in the hippocampus. These findings suggest that Bay 60-7550 protects mice against PTSD-like stress induced traumatic injury by activation of cGMP- or cAMP-related neuroprotective molecules, such as synaptic proteins, pCREB and BDNF.