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1.
Psychosomatics ; 61(6): 597-606, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32800347

RESUMO

BACKGROUND: Chloroquine and hydroxychloroquine are among several experimental treatments being investigated in the urgent response to the coronavirus disease-2019. With increased use of these medications, physicians need to become knowledgeable of these drugs' neuropsychiatric side effects and interactions with psychiatric medications. OBJECTIVE: Clarify evidence base regarding the psychiatric side effects and psychiatric drug interactions of chloroquine and hydroxychloroquine. METHODS: A literature review was performed in PubMed from 1950 to 2020 regarding psychiatric topics and targeted pharmacological properties of chloroquine and hydroxychloroquine. RESULTS: First, chloroquine and hydroxychloroquine may mildly inhibit CYP2D6 metabolism of psychiatric medications, and psychiatric medications that interfere with CYP2D6 or CYP3A4 activity could alter chloroquine and hydroxychloroquine levels. Second, they may prolong the QT interval, warranting caution with concomitant prescription of other QT prolonging agents. Finally, neuropsychiatric side effects are very uncommon but possible and include a potentially prolonged phenomenon of "psychosis after chloroquine." Hydroxychloroquine has less information available about its neuropsychiatric side effects than chloroquine, with psychosis literature limited to several case reports. Weak evidence suggests a possible association of hydroxychloroquine exposure and increased suicidal ideation. It is not clear whether patients with psychiatric illness are more vulnerable to neuropsychiatric sequela of these medications; however, overdose of these medications by suicidal patients has high risk of mortality. CONCLUSION: The risk of neuropsychiatric side effects of chloroquine and hydroxychloroquine when used for coronavirus disease-2019 treatment is not known. Best practice may include suicide risk assessment for patients treated with hydroxychloroquine. However, delirium is expected to be a more likely etiology of neuropsychiatric symptoms in critically ill patients treated for coronavirus disease-2019, and adjustment disorder is a much more likely etiology of anxiety and depression symptoms than the side effects of chloroquine or hydroxychloroquine.


Assuntos
Antivirais/efeitos adversos , Cloroquina/efeitos adversos , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/efeitos adversos , Pneumonia Viral/tratamento farmacológico , Psicotrópicos/efeitos adversos , Antivirais/uso terapêutico , Ansiedade/induzido quimicamente , Betacoronavirus , Transtorno Bipolar/induzido quimicamente , Cloroquina/uso terapêutico , Inibidores do Citocromo P-450 CYP2D6/efeitos adversos , Indutores do Citocromo P-450 CYP3A/efeitos adversos , Transtorno Depressivo/induzido quimicamente , Interações Medicamentosas , Cefaleia/induzido quimicamente , Humanos , Hidroxicloroquina/uso terapêutico , Síndrome do QT Longo/induzido quimicamente , Transtornos Neurocognitivos/induzido quimicamente , Pandemias , Psicoses Induzidas por Substâncias/etiologia , Psicotrópicos/uso terapêutico
2.
Psiquiatr. biol. (Internet) ; 27(2): 54-60, mayo-ago. 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-193247

RESUMO

En los pacientes con trastorno bipolar existe una elevada prevalencia de consumo de drogas, siendo el cannabis una de las principales. El consumo puede modificar las manifestaciones clínicas y la evolución del trastorno. El objetivo del presente trabajo es estudiar la influencia del consumo de cannabis sobre la evolución del trastorno bipolar. Se ha realizado una revisión sistemática realizando una búsqueda de artículos en Medline. Se han obtenido 5 artículos sobre cohortes de sujetos bipolares que estudian el efecto de dicho consumo. El consumo de cannabis se presenta como un factor pronóstico negativo, con menor recuperación clínica, peor funcionamiento global, más tiempo en episodios afectivos y, posiblemente, mayor frecuencia de ciclos rápidos y episodios maníacos o mixtos. El cese del consumo mejora la evolución. El consumo de otras drogas es frecuente entre los consumidores de cannabis y se asocia a una evolución negativa


Bipolar disorder patients have a high prevalence of drug use, being cannabis one of the main drugs involved. Cannabis use can modify clinical characteristics and outcome of this disorder. The aim of the current work is to evaluate from longitudinal studies the influence of cannabis use in the outcome of bipolar disorder. A systematic review was carried out through a Medline searching. 5 papers were found on bipolar patients cohorts that study this effect. Cannabis use is a negative prognostic factor, it was associated with less sucessful clinical recovery, worse global functioning, more time in affective episodes, and probably, more often rapid cycling and manic/mixed episodes. Bipolar patients who stop using cannabis show a better outcome. Alcohol and other drugs use are common between cannabis users and are associated with a negative outcome


Assuntos
Humanos , Masculino , Feminino , Abuso de Maconha/complicações , Transtorno Bipolar/induzido quimicamente , Transtorno Bipolar/fisiopatologia
3.
Braz J Psychiatry ; 42(5): 481-488, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32401870

RESUMO

OBJECTIVES: To prospectively investigate whether baseline clinical characteristics and medication exposure predict development of major depressive disorder or bipolar disorder in offspring of parents with bipolar disorder. METHODS: Youth aged 9-20 years with at least one biological parent with bipolar disorder and no prior history of mood or psychotic episodes (n=93) were prospectively evaluated and treated naturalistically during the study. Participants were divided into two groups: converters, defined as those who met DSM-IV criteria for a mood episode during follow-up (n=19); or non-converters (n=74). Logistic regression models were used to investigate associations between baseline clinical variables and medication exposure during follow-up and risk of developing a first mood episode (conversion). RESULTS: Multivariate regression analyses showed that baseline anxiety disorders and subsyndromal mood disorders were associated with increased risk of conversion during follow-up. Adding medication exposure to the multivariate model showed that exposure to antidepressants during follow-up was associated with increased risk of conversion. CONCLUSIONS: Caution should be used when treating bipolar offspring with anxiety and/or emerging depressive symptoms using antidepressant agents, given the increased risk of developing a major mood disorder.


Assuntos
Transtorno Bipolar , Transtorno Depressivo Maior , Adolescente , Adulto , Transtorno Bipolar/induzido quimicamente , Transtorno Bipolar/tratamento farmacológico , Criança , Manual Diagnóstico e Estatístico de Transtornos Mentais , Humanos , Pais , Estudos Prospectivos , Adulto Jovem
4.
Rev. psiquiatr. infanto-juv ; 37(1): 34-41, ene.-mar. 2020.
Artigo em Espanhol | IBECS | ID: ibc-193563

RESUMO

Ante un cambio radical en el comportamiento en un varón de 17 años, a las 12 horas de administrar, en el mismo día, las vacunas contra el Meningococo C, Hepatitis B, Triple Vírica y Varicela, y la detección de un cuadro maníaco a la semana, se sospechó que se tratase de un cuadro de encefalitis post-vacunal. A pesar de la ausencia de hallazgos patológicos en las exploraciones complementarias realizadas, y aunque en la literatura científica no se haya demostrado una asociación temporal a día de hoy, no podemos aceptar ni descartar con certeza la sospecha diagnóstica dado que no contamos con la serología infecciosa o un estudio de anticuerpos en líquido cefalorraquídeo. Los efectos secundarios graves tras vacunaciones no han quedado claramente demostrados, lo que sí está ampliamente demostrado es que la inmunidad adquirida es uno de los mayores logros de la medicina que ha ayudado a erradicar enfermedades potencialmente mortales


A radical behavioral change was observed in a 17-year-old male 12 hours after having received vaccines for Meningococcus C, Hepatitis B, Triple Viral and Varicella on the same day. Moreover a manic episode was detected one week later. It was suspected that this was a case of post-vaccinal encephalitis. In spite of the absence of pathological findings in the complementary explorations carried out and although a temporal association has not been demonstrated to date in the scientific literature, we can not be certain of this diagnostic suspicion since we do not have the infectious serology or a study of antibodies in central spinal fluid. Serious side effects after vaccinations have never been clearly demonstrated, while it has been widely demonstrated that the acquired immunity from these vaccines is one of the greatest achievements of medicine, and this has helped to eradicate life-threatening diseases


Assuntos
Humanos , Masculino , Adolescente , Transtorno Bipolar/induzido quimicamente , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Vacinas Virais/efeitos adversos , Transtorno Bipolar/psicologia , Neisseria meningitidis Sorogrupo C/imunologia , Hepatite B/imunologia , Vacina contra Varicela/efeitos adversos , Psicopatologia/métodos
6.
Food Chem Toxicol ; 136: 110986, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31760073

RESUMO

It is recognized that d-amphetamine (AMPH)-induced hyperactivity is thought to be a valid animal model of mania. In the present study, we investigated whether a proinflammatory oxidative gene indoleamine-2,3-dioxygenase (IDO) is involved in AMPH-induced mitochondrial burden, and whether mood stabilizers (i.e., lithium and valproate) modulate IDO to protect against AMPH-induced mania-like behaviors. AMPH-induced IDO-1 expression was significantly greater than IDO-2 expression in the prefrontal cortex of wild type mice. IDO-1 expression was more pronounced in the mitochondria than in the cytosol. AMPH treatment activated intra-mitochondrial Ca2+ accumulation and mitochondrial oxidative burden, while inhibited mitochondrial membrane potential and activity of the mitochondrial complex (I > II), mitochondrial glutathione peroxidase, and superoxide dismutase, indicating that mitochondrial burden might be contributable to mania-like behaviors induced by AMPH. The behaviors were significantly attenuated by lithium, valproate, or IDO-1 knockout, but not in IDO-2 knockout mice. Lithium, valproate administration, or IDO-1 knockout significantly attenuated mitochondrial burden. Neither lithium nor valproate produced additive effects above the protective effects observed in IDO-1 KO in mice. Collectively, our results suggest that mood stabilizers attenuate AMPH-induced mania-like behaviors via attenuation of IDO-1-dependent mitochondrial stress, highlighting IDO-1 as a novel molecular target for the protective potential of mood stabilizers.


Assuntos
Antimaníacos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Lítio/uso terapêutico , Ácido Valproico/uso terapêutico , Animais , Transtorno Bipolar/induzido quimicamente , Transtorno Bipolar/metabolismo , Cálcio/metabolismo , Dextroanfetamina , Glutationa Peroxidase/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Locomoção/efeitos dos fármacos , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Córtex Pré-Frontal/patologia , Superóxido Dismutase/metabolismo
8.
Psiquiatr. biol. (Internet) ; 26(3): 99-104, sept.-dic. 2019. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-191660

RESUMO

OBJETIVOS: Evaluar si los inhibidores de la colinesterasa pueden inducir manía, y determinar si este efecto puede estar relacionado con estados u otras características previas de los pacientes. MÉTODO: Se realizó una revisión sistemática, incluyendo artículos publicados en ISI Web of Knowledge y PubMed, desde enero de 1990 a marzo de 2018, siguiendo criterios PRISMA. RESULTADOS: De 326 estudios identificados, se incluyeron en la revisión 16. En los casos comunicados hay una correlación entre la introducción de un inhibidor de la colinesterasa y la aparición de un episodio maníaco/hipomaníaco. El riesgo parece ser mayor si el paciente tiene antecedentes de trastorno afectivo y si está tomando medicación antidepresiva. CONCLUSIONES: Los inhibidores de la colinesterasa pueden inducir manía en algunos pacientes. Más estudios son necesarios para una mejor comprensión de este fenómeno; se deben tomar precauciones al prescribir estos fármacos en pacientes de riesgo


AIMS: To evaluate if cholinesterase inhibitors can induce mania, and if so to determine if this effect could be related to pre-existing conditions and other patient characteristics. METHODS: A systematic review was conducted that included articles published in PubMed and ISI Web of Knowledge from January 1990 to March 2018, following PRISMA guidelines. RESULTS: From a total of 326 studies found, 16 were included in the review. In the reported cases, there was a correlation between the introduction of a cholinesterase inhibitor and the development of a manic/ hypomanic episode. The risk appears to be higher if the patient had a history of affective disorder and if he/she was taking antidepressant medication. CONCLUSIONS: Cholinesterase inhibitors may induce mania in some patients. Further studies are needed for a better understanding of this phenomenon. Care should be taken when prescribing these drugs in specific patients


Assuntos
Masculino , Humanos , Feminino , Inibidores da Colinesterase/efeitos adversos , Transtorno Bipolar/induzido quimicamente , Donepezila/efeitos adversos , Galantamina/efeitos adversos , Rivastigmina/efeitos adversos , Fatores de Risco
9.
Psiquiatr. biol. (Internet) ; 26(3): 123-126, sept.-dic. 2019. tab
Artigo em Espanhol | IBECS | ID: ibc-191665

RESUMO

Se ha descrito que los medicamentos antiinflamatorios no esteroideos (AINE) tienen la capacidad para inducir o agravar cuadros psiquiátricos como los trastornos de ansiedad, la depresión o los trastornos psicóticos. Por otra parte, el trastorno bipolar inducido por sustancias o medicamentos es un trastorno del estado de ánimo que se caracteriza por una brusca aparición de los síntomas como consecuencia de la intoxicación, abstinencia o exposición a una sustancia capaz de inducir una sintomatología específica, concretamente, una elevación persistente en el estado de ánimo o irritabilidad que puede ir acompañado de un estado de ánimo deprimido o un interés o placer disminuido en la mayoría de las actividades. Describimos el caso clínico de una paciente que fue diagnosticada de trastorno bipolar inducido por medicamentos tras haber recibido tratamiento en las semanas previas con celecoxib


Non-steroidal anti-inflammatory drugs (NSAIDs) have the ability to induce or aggravate psychiatric conditions such as anxiety, depression or psychotic disorders. On the other hand, substance/medication-induced bipolar disorder is a mood disorder characterized by a sudden onset of symptoms as a result of intoxication, abstinence or exposure to a substance capable of inducing a specific symptomatology, specifically, a persistent elevation in mood or irritability that may be accompanied by a depressed mood or decreased interest or pleasure in most activities. We describe the clinical case of a patient who was diagnosed with medication-induced bipolar disorder after receiving treatment in the previous weeks with celecoxib


Assuntos
Adulto , Humanos , Feminino , Transtorno Bipolar/induzido quimicamente , Celecoxib/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Dor Crônica/tratamento farmacológico , Celecoxib/uso terapêutico
10.
Transl Psychiatry ; 9(1): 297, 2019 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-31723123

RESUMO

The present study intends to investigate the effect of lithium (Li) and celecoxib (Cel) coadministration on the behavioral status and oxidative stress parameters in a rat model of mania induced by dextroamphetamine (d-AMPH). Male Wistar rats were treated with d-AMPH or saline (Sal) for 14 days; on the 8th day of treatment, rats received lithium (Li), celecoxib (Cel), Li plus Cel, or water until day 14. Levels of oxidative stress parameters were evaluated in the serum, frontal cortex, and hippocampus. d-AMPH administration induced hyperlocomotion in rats, which was significantly reversed by Li and Cel coadministration. In addition, d-AMPH administration induced damage to proteins and lipids in the frontal cortex and hippocampus of rats. All these impairments were reversed by treatment with Li and/or Cel, in a way dependent on cerebral area and biochemical analysis. Li and Cel coadministration reversed the d-AMPH-induced decrease in catalase activity in cerebral structures. The activity of glutathione peroxidase was decreased in the frontal cortex of animals receiving d-AMPH, and treatment with Li, Cel, or a combination thereof reversed this alteration in this structure. Overall, data indicate hyperlocomotion and alteration in oxidative stress biomarkers in the cerebral structures of rats receiving d-AMPH. Li and Cel coadministration can mitigate these modifications, comprising a potential novel approach for BD therapy.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Antimaníacos/uso terapêutico , Comportamento Animal/efeitos dos fármacos , Transtorno Bipolar/tratamento farmacológico , Celecoxib/uso terapêutico , Compostos de Lítio/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Antimaníacos/administração & dosagem , Transtorno Bipolar/induzido quimicamente , Celecoxib/administração & dosagem , Dextroanfetamina/administração & dosagem , Modelos Animais de Doenças , Dopamina/metabolismo , Quimioterapia Combinada , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Compostos de Lítio/administração & dosagem , Masculino , Atividade Motora/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar
12.
BMJ Case Rep ; 12(11)2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31678927

RESUMO

Isoniazid preventative therapy is widely used for latent tuberculosis infection. Isoniazid is highly effective but has many adverse effects, including neuropsychiatric. We describe the case of an 80-year-old woman with mania. She had received isoniazid preventative therapy during steroid treatment for rheumatoid arthritis and organising pneumonia for the previous 5 months. Her mania resolved after discontinuation of isoniazid. Adverse effects of isoniazid should be considered even if a long time has elapsed since the start of administration. Physicians other than infectious disease and respiratory specialists also must be aware of the adverse effects of isoniazid preventative therapy.


Assuntos
Antituberculosos/efeitos adversos , Transtorno Bipolar/induzido quimicamente , Isoniazida/efeitos adversos , Tuberculose Latente/prevenção & controle , Idoso de 80 Anos ou mais , Antituberculosos/administração & dosagem , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Feminino , Humanos , Isoniazida/administração & dosagem , Pneumonia/complicações , Pneumonia/tratamento farmacológico
13.
Sci Rep ; 9(1): 15627, 2019 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-31666560

RESUMO

Intracerebroventricular (ICV) administration of ouabain, an inhibitor of the Na, K-ATPase, is an approach used to study the physiological functions of the Na, K-ATPase and cardiotonic steroids in the central nervous system, known to cause mania-like hyperactivity in rats. We describe a mouse model of ouabain-induced mania-like behavior. ICV administration of 0.5 µl of 50 µM (25 pmol, 14.6 ng) ouabain into each lateral brain ventricle results in increased locomotor activity, stereotypical behavior, and decreased anxiety level an hour at minimum. Fast-scan cyclic voltammetry showed that administration of 50 µM ouabain causes a drastic drop in dopamine uptake rate, confirmed by elevated concentrations of dopamine metabolites detected in the striatum 1 h after administration. Ouabain administration also caused activation of Akt, deactivation of GSK3ß and activation of ERK1/2 in the striatum of ouabain-treated mice. All of the abovementioned effects are attenuated by haloperidol (70 µg/kg intraperitoneally). Observed effects were not associated with neurotoxicity, since no dystrophic neuron changes in brain structures were demonstrated by histological analysis. This newly developed mouse model of ouabain-induced mania-like behavior could provide a perspective tool for studying the interactions between the Na,K-ATPase and the dopaminergic system.


Assuntos
Transtorno Bipolar/induzido quimicamente , Ouabaína/efeitos adversos , Receptores de Dopamina D2/metabolismo , Animais , Comportamento Animal , Transtorno Bipolar/genética , Transtorno Bipolar/metabolismo , Transtorno Bipolar/psicologia , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Modelos Animais de Doenças , Dopamina/metabolismo , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Masculino , Camundongos , Ouabaína/administração & dosagem , Receptores de Dopamina D2/genética , ATPase Trocadora de Sódio-Potássio/genética , ATPase Trocadora de Sódio-Potássio/metabolismo
14.
J Opioid Manag ; 15(4): 342-344, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31637686

RESUMO

A 49-year-old male with major depressive disorder well-managed with venlafaxine [serotonin and norepinephrine reuptake inhibitor (SNRI)] and no history of manic episodes developed his first manic episode following use of tramadol. Tramadol-induced mania has been described with selective serotonin reuptake inhibitors but not SNRIs. In addition, mania is not listed as a potential clinical side effect-further illustrating this relative rarity. Due to tramadol's SNRI activity, there is definitive risk for mood lability in individuals managed with tramadol and other serotonergic medications as seen in this patient. The authors findings suggest the need for greater risk consideration when prescribing tramadol with other related agents such as venlafaxine.


Assuntos
Transtorno Bipolar , Transtorno Depressivo Maior , Tramadol , Cloridrato de Venlafaxina , Analgésicos Opioides , Transtorno Bipolar/induzido quimicamente , Transtorno Depressivo Maior/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores de Captação de Serotonina/efeitos adversos , Tramadol/efeitos adversos , Tramadol/uso terapêutico , Cloridrato de Venlafaxina/efeitos adversos , Cloridrato de Venlafaxina/uso terapêutico
15.
Acta Med Port ; 32(10): 671-673, 2019 Oct 01.
Artigo em Português | MEDLINE | ID: mdl-31625880

RESUMO

Manic and hypomanic states associated with antidepressant treatments are relatively common; however, when specifically considering mirtazapine, those side effects are infrequent. The authors report a clinical case regarding a manic episode with dysphoric features in a patient with no personal or family previous psychiatric history. It began two weeks after starting treatment with mirtazapine up to 30 mg/day. This episode was treated discontinuing mirtazapine and initiating olanzapine (10 mg), with symptomatic remission. Mirtazapine has a specific pharmacodynamics, blocking not only post-synaptic serotonergic receptors but also α2-presynaptic adrenergic receptors. Taking this into consideration, it was hypothesized that this case could be attributed to a noradrenergic syndrome, characterized by dysphoria, irritability, insomnia and psychomotor agitation.


Assuntos
Antidepressivos/efeitos adversos , Transtorno Bipolar/induzido quimicamente , Mirtazapina/efeitos adversos , Psicoses Induzidas por Substâncias/etiologia , Antidepressivos/farmacocinética , Antipsicóticos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Mirtazapina/farmacocinética , Olanzapina/uso terapêutico
16.
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; 41(5): 419-427, Sept.-Oct. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1039115

RESUMO

Objective: To evaluate whether an animal model of mania induced by lisdexamfetamine dimesylate (LDX) has an inflammatory profile and whether immune activation by lipopolysaccharides (LPS) has a cumulative effect on subsequent stimuli in this model. We also evaluated the action of lithium (Li) on inflammatory and neurotrophic factors. Methods: Adult male Wistar rats were subjected to an animal model of mania. After the open-field test, they were given LPS to induce systemic immune activation. Subsequently, the animals' blood was collected, and their serum levels of brain-derived neurotrophic factor and inflammatory markers (tumor necrosis factor [TNF]-α, interleukin [IL]-6, IL-1β, IL-10, and inducible nitric oxide synthase [iNOS]) were measured. Results: LDX induced hyperactivity in the animals, but no inflammatory marker levels increased except brain-derived neurotrophic factor (BDNF). Li had no effect on serum BDNF levels but prevented iNOS levels from increasing in animals subjected to immune activation. Conclusion: Although Li prevented an LPS-induced increase in serum iNOS levels, its potential anti-inflammatory effects in this animal model of mania were conflicting.


Assuntos
Animais , Masculino , Transtorno Bipolar/imunologia , Modelos Animais de Doenças , Dimesilato de Lisdexanfetamina , Lítio/farmacologia , Anti-Inflamatórios/farmacologia , Fatores de Crescimento Neural/efeitos dos fármacos , Fatores de Tempo , Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/induzido quimicamente , Ensaio de Imunoadsorção Enzimática , Lipopolissacarídeos/farmacologia , Reprodutibilidade dos Testes , Citocinas/sangue , Resultado do Tratamento , Ratos Wistar , Fator Neurotrófico Derivado do Encéfalo/sangue , Óxido Nítrico Sintase Tipo II/sangue , Locomoção/efeitos dos fármacos
18.
Transl Psychiatry ; 9(1): 158, 2019 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-31164628

RESUMO

A particular challenge in the development of a bipolar disorder (BD) model in animals is the complicated clinical course of the condition, characterized by manic, depressive and mixed mood episodes. Ouabain (OUA) is an inhibitor of Na+/K+-ATPase enzyme. Intracerebroventricular (ICV) injection of this drug in rats has been regarded a proper model to study BD by mimic specific manic symptoms, which are reversed by lithium (Li), an important mood stabilizer drug. However, further validation of this experimental approach is required to characterize it as an animal model of BD, including depressive-like behaviors. The present study aimed to assess manic- and depressive-like behaviors, potential alteration in the hypothalamic-pituitary-adrenal (HPA) system and oxidative stress parameters after a single OUA ICV administration in adult male Wistar rats. Moreover, we evaluated Li effects in this experimental setting. Data show that OUA ICV administration could constitute a suitable model for BD since the injection of the drug triggered manic- and depressive-like behaviors in the same animal. Additionally, the OUA model mimics significant physiological and neurochemical alterations detected in BD patients, including an increase in oxidative stress and change in HPA axis. Our findings suggest that decreased Na+/K+-ATPase activity detected in bipolar patients may be linked to increased secretion of glucocorticoid hormones and oxidative damage, leading to the marked behavioral swings. The Li administration mitigated these pathological changes in the rats. The proposed OUA model is regarded as suitable to simulate BD by complying with all validities required to a proper animal model of the psychiatric disorder.


Assuntos
Comportamento Animal/efeitos dos fármacos , Transtorno Bipolar/induzido quimicamente , Transtorno Bipolar/fisiopatologia , Modelos Animais de Doenças , Inibidores Enzimáticos/farmacologia , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Ouabaína/farmacologia , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Animais , Antimaníacos/farmacologia , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/fisiopatologia , Injeções Intraventriculares , Compostos de Lítio/farmacologia , Masculino , Sistema Hipófise-Suprarrenal/metabolismo , Sistema Hipófise-Suprarrenal/fisiopatologia , Ratos Wistar
19.
Pharmacol Biochem Behav ; 183: 56-63, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31158395

RESUMO

The present study evaluated the effects of the coadministration of lithium (Li) and Cel on inflammatory parameters in an animal model of mania induced by dextroamphetamine (D-amph). It was used Wistar rats 60 days old (250-350 g). The animals (n = 10 per group) received D-amph (2 mg/kg) or saline solution of NaCl 0.9% (Sal) intraperitoneally once a day for 14 days. From day eight until 14, the animals from the D-amph and Sal groups received Li (24 mg/kg), Cel (20 mg/kg), Li + Cel or water via gavage. Behavioral analyses were performed using the open-field test. The levels of IL-1ß, IL-4, IL-10, and TNF-α were evaluated. The administration of D-amph induced hyperactivity in the rats, as well increased the IL-4, IL-10, and TNF-α levels in the serum, frontal cortex, and striatum of rats compared to those of the controls, and treatment with Li plus Cel reversed these alterations. In general, the administration of Li or Cel per se did not have effects on the behavioral and biochemical parameters. However, the treatment with Cel per se decreased only the IL-10 levels in the serum of animals. Besides, the treatment with Li or Cel decreased the IL-4 levels in the serum and reversed the effects of D-amph on this parameter in the frontal cortex. The treatment with Li reversed the effects of D-amph on the TNF-α levels in all tissues evaluated, and the administration of Cel reversed this alteration only in the striatum. It can be observed that treatment with Li plus Cel was more effective against damages caused by D-amph when compared to the administration of both treatments per se, suggesting that the coadministration can be more effective to treat BD rather than Li or Cel itself. The treatment with Li plus Cel was effective against the inflammation induced by D-amph.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Antimaníacos/uso terapêutico , Comportamento Animal/efeitos dos fármacos , Transtorno Bipolar/induzido quimicamente , Transtorno Bipolar/tratamento farmacológico , Celecoxib/uso terapêutico , Dextroanfetamina/farmacologia , Compostos de Lítio/uso terapêutico , Análise de Variância , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Antimaníacos/administração & dosagem , Celecoxib/administração & dosagem , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Citocinas/metabolismo , Dextroanfetamina/administração & dosagem , Modelos Animais de Doenças , Quimioterapia Combinada , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/metabolismo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Compostos de Lítio/administração & dosagem , Masculino , Ratos , Ratos Wistar
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