RESUMO
OBJECTIVE: Methylphenidate hydrochloride is the most widely used medication for treatment and management of attention-deficit hyperactivity disorder. However, the chronic effects of methylphenidate hydrochloride on anxiety- and depressive-like rat behaviors remain poorly investigated. In this context, the present study evaluated the effects of treatment with methylphenidate hydrochloride on anxiety- and depressive-like behaviors using young and adult rats during the light and the dark cycle. METHOD: Male Wistar rats (25 or 60 days old) received a once-daily (in either the light or dark cycle) methylphenidate hydrochloride (2mg/kg) or saline intraperitoneal injection for 28 days. We performed elevated plus maze and forced swimming test two hours after the last injection. RESULTS: The light/dark cycle was a significant factor in the anxiety-like behaviors; however, no significant interaction between all three factors (cycle, age and methylphenidate hydrochloride) was found. Nevertheless, we observed a nominally significant interaction between the light/ dark cycle and age in the forced swimming test. CONCLUSION: Our results have shown that age and the light/dark cycle are more significant modulators of anxiety- and depressive-like behaviors than methylphenidate hydrochloride treatment.
OBJETIVO: Hidrocloridrato de metilfenidato é a medicação preferida para o tratamento e manutenção do transtorno de atenção e hiperatividade. No entanto, os efeitos do tratamento crônico com hidrocloridrato de metilfenidato em diferentes idades e ciclos sobre o comportamento relacionado à ansiedade e à depressão ainda não está claro. Neste contexto, o presente estudo teve como objetivo avaliar os efeitos do tratamento com hidrocloridrato de metilfenidato sobre o comportamento relacionado à ansiedade e à depressão em diferentes idades e no ciclo claro e escuro. MÉTODO: Foram utilizados ratos Wistar machos jovens e adultos que receberam uma vez ao dia (ciclo claro e escuro) hidrocloridrato de metilfenidato (2mg/kg) ou salina com injeção intraperitoneal, durante 28 dias. Após duas horas da última injeção, os animais foram submetidos ao testes de labirinto em cruz elevada e natação forçada. RESULTADOS: A fase do ciclo claro e escuro foi um fator significativo para o comportamento relacionado à ansiedade. Além disso, não houve interação significativa entre os ciclos claro e escuro, idade e metilfenidato no comportamento relacionado à ansiedade e à depressão, mas foi observada uma interação significativa entre ciclo claro e escuro e idade no teste de natação forçada. CONCLUSÃO: Nossos resultados mostraram que a idade e o ciclo claro e escuro são moduladores significativos de ambos os comportamentos quanto do tratamento com hidrocloridrato de metilfenidato.
Assuntos
Animais , Masculino , Ratos , Ansiolíticos/uso terapêutico , Antidepressivos/uso terapêutico , Transtornos de Ansiedade/tratamento farmacológico , Transtorno Depressivo/tratamento farmacológico , Metilfenidato/uso terapêutico , Fotoperíodo , Fatores Etários , Transtornos de Ansiedade/psicologia , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno Depressivo/psicologia , Ratos WistarRESUMO
OBJECTIVE: Methylphenidate hydrochloride is the most widely used medication for treatment and management of attention-deficit hyperactivity disorder. However, the chronic effects of methylphenidate hydrochloride on anxiety- and depressive-like rat behaviors remain poorly investigated. In this context, the present study evaluated the effects of treatment with methylphenidate hydrochloride on anxiety- and depressive-like behaviors using young and adult rats during the light and the dark cycle. METHOD: Male Wistar rats (25 or 60 days old) received a once-daily (in either the light or dark cycle) methylphenidate hydrochloride (2mg/kg) or saline intraperitoneal injection for 28 days. We performed elevated plus maze and forced swimming test two hours after the last injection. RESULTS: The light/dark cycle was a significant factor in the anxiety-like behaviors; however, no significant interaction between all three factors (cycle, age and methylphenidate hydrochloride) was found. Nevertheless, we observed a nominally significant interaction between the light/ dark cycle and age in the forced swimming test. CONCLUSION: Our results have shown that age and the light/dark cycle are more significant modulators of anxiety- and depressive-like behaviors than methylphenidate hydrochloride treatment.
Assuntos
Ansiolíticos/uso terapêutico , Antidepressivos/uso terapêutico , Transtornos de Ansiedade/tratamento farmacológico , Transtorno Depressivo/tratamento farmacológico , Metilfenidato/uso terapêutico , Fotoperíodo , Fatores Etários , Animais , Transtornos de Ansiedade/psicologia , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno Depressivo/psicologia , Masculino , Ratos , Ratos WistarRESUMO
Methylphenidate (MPH) is a very effective treatment option for children and adolescents with attention-deficit/hyperactivity disorder. Nevertheless, there have been inconsistent reports regarding the effects of MPH on learning and memory. The aim of this study was to evaluate whether the treatment with MPH during the morning differs from that during the night on learning and memory (short and long term) in young and adult male Wistar rats. The animals received once daily intraperitoneal injection of either MPH (2 mg/kg) or saline (0.9%) for 28 days (either in the morning or at night). The animals underwent two behavioral tasks to evaluate learning and memory: inhibitory avoidance task and continuous multiple trials step-down inhibitory avoidance (CMIA). Young rats treated in the morning showed significant impaired long-term memory for inhibitory avoidance training and facilitated acquisition in the CMIA. Adult rats treated in the night showed impaired long-term retention in the CMIA. We observed similar performances in both tests for young rats treated at night or adult rats treated in the morning. Our results suggest that age and time of treatment can alter the MPH effects in learning and memory.
Assuntos
Envelhecimento , Aprendizagem da Esquiva/efeitos dos fármacos , Memória/efeitos dos fármacos , Metilfenidato/administração & dosagem , Nootrópicos/administração & dosagem , Fotoperíodo , Animais , Aprendizagem da Esquiva/fisiologia , Injeções Intraperitoneais , Masculino , Memória/fisiologia , Memória de Curto Prazo/efeitos dos fármacos , Memória de Curto Prazo/fisiologia , Testes Neuropsicológicos , Ratos , Ratos Wistar , Fatores de TempoRESUMO
In this study age-, circadian rhythm- and methylphenidate administration- effect on open field habituation and object recognition were analyzed. Young and adult male Wistar rats were treated with saline or methylphenidate 2.0 mg/kg for 28 days. Experiments were performed during the light and the dark cycle. Locomotor activity was significantly altered by circadian cycle and methylphenidate treatment during the training session and by drug treatment during the testing session. Exploratory activity was significantly modulated by age during the training session and by age and drug treatment during the testing session. Object recognition memory was altered by cycle at the training session; by age 1.5 h later and by cycle and age 24 h after the training session. These results show that methylphenidate treatment was the major modulator factor on open-field test while cycle and age had an important effect on object recognition experiment.
Assuntos
Envelhecimento/fisiologia , Estimulantes do Sistema Nervoso Central/farmacologia , Ritmo Circadiano/fisiologia , Metilfenidato/farmacologia , Desempenho Psicomotor/efeitos dos fármacos , Reconhecimento Psicológico/efeitos dos fármacos , Animais , Aprendizagem/efeitos dos fármacos , Masculino , Memória de Curto Prazo/efeitos dos fármacos , Atividade Motora/fisiologia , Ratos , Ratos WistarRESUMO
Dopamine may alter the phosphorylation state of DARPP-32 that plays a central role in the dopaminergic neurons biology. Studies have shown that DARPP-32/protein phosphatase 1 cascade is a major target for psychostimulants drugs. Methylphenidate is a psychostimulant that acts blocking the dopamine transporter has been used as an effective treatment for Attention Deficit Hyperactivity Disorder. We investigated if methylphenidate could alter DARPP-32 expression in five brain regions (striatum, hippocampus, prefrontal cortex, cortex and cerebellum) in young and adult rats. Our results showed that methylphenidate treatment is able to alter DARPP-32 expression in rat brain. Acute methylphenidate treatment has reduced hippocampal DARPP-32 protein levels in old rats, while chronic methylphenidate treatment has decreased them in old rat hippocampus and young rat cerebellum. It was found an increased cortical expression after chronic methylphenidate administration in old rats. Our results provide the first experimental demonstration that methylphenidate induces changes in total DARPP-32 expression that are posology- and age-related in some rat brain areas, although further studies are needed to shed more light on the mechanisms behind these findings.
Assuntos
Envelhecimento/fisiologia , Encéfalo/efeitos dos fármacos , Fosfoproteína 32 Regulada por cAMP e Dopamina/efeitos dos fármacos , Metilfenidato/farmacologia , Animais , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/metabolismo , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Estimulantes do Sistema Nervoso Central/farmacologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/crescimento & desenvolvimento , Córtex Cerebral/metabolismo , Dopamina/metabolismo , Fosfoproteína 32 Regulada por cAMP e Dopamina/metabolismo , Esquema de Medicação , Hipocampo/efeitos dos fármacos , Hipocampo/crescimento & desenvolvimento , Hipocampo/metabolismo , Ratos , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologiaRESUMO
Several species of Passiflora have been employed widely as a folk medicine because of sedative and tranquillizer activities. In this study, we evaluate the effects on anxiety and memory process of two popularly used Passiflora species. To this aim, male Wistar rats (weighing 250-300 g) were intraperitoneally injected with the aqueous extract of Passiflora alata or Passiflora edulis (25, 50, 100, or 150 mg/kg; single injection) 30 minutes prior to the elevated plus-maze test, inhibitory avoidance test, or habituation to an open-field apparatus. The effects of both species of Passiflora were compared with that of diazepam (1 mg/kg), a standard anxiolytic drug. Our findings revealed that, similar to diazepam, the treatment with P. alata (100 and 150 mg/kg) and P. edulis (50, 100, and 150 mg/kg) induced anxiolytic-like effects in rats. Memory was not affected by the treatment with any dose of P. alata or P. edulis, but diazepam disrupted memory process in rats. Phytochemical analysis showed that the content of flavonoids of the aqueous extract of P. edulis is almost twice that of P. alata. These differences in contents of flavonoids could explain the lower active doses of the aqueous extract of P. edulis in inducing anxiolytic-like effects compared to P. alata. In conclusion, our findings suggest that, distinct from diazepam, the aqueous extract of both species of Passiflora induced anxiolytic-like effects in rats without disrupting memory process.
Assuntos
Ansiedade/tratamento farmacológico , Memória/efeitos dos fármacos , Passiflora/química , Fitoterapia , Extratos Vegetais/administração & dosagem , Animais , Ansiolíticos/uso terapêutico , Aprendizagem da Esquiva/efeitos dos fármacos , Diazepam/efeitos adversos , Diazepam/uso terapêutico , Flavonoides/administração & dosagem , Flavonoides/análise , Injeções Intraperitoneais , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Extratos Vegetais/efeitos adversos , Ratos , Ratos Wistar , ÁguaRESUMO
Typical and atypical antipsychotic drugs have been shown to have different clinical and behavioral profiles. Haloperidol (HAL) is a typical neuroleptic that acts primarily as a D(2) dopamine receptor antagonist. It has been proposed that reactive oxygen species play a causative role in neurotoxic effects induced by HAL. We evaluated oxidative damage in rat brain induced by chronic (28 days) HAL, clozapine (CLO), olanzapine (OLZ) or aripiprazole (ARI) administration. Adult male Wistar rats received daily injections of HAL (1.5 mg/kg), CLO (25 mg/kg), OLZ (2.5, 5 or 10 mg/kg) or ARI (2, 10 or 20 mg/kg); control animals received vehicle (Tween 1% solution). Thiobarbituric acid reactive substances (TBARS) and protein carbonylation were measured in the prefrontal cortex, hippocampus, striatum and cerebral cortex. The results showed that TBARS were increased in the striatum after HAL treatment. On the other hand, TBARS were diminished in the prefrontal cortex by OLZ and ARI. Our results also showed that all drugs tested in this work decreased TBARS levels in the cerebral cortex. In hippocampus, TBARS levels were not altered by any drug. Protein carbonyl content after HAL and CLO treatment was increased in the hippocampus. Moreover, OLZ and ARI did not alter protein carbonyl content when compared to control group. ARI chronic administration (20 mg/kg) also increased mitochondrial superoxide in the prefrontal cortex and striatum. ARI did not alter mitochondrial superoxide in the hippocampus and cerebral cortex. Moreover, HAL, OLZ and CLO did not cause significant alterations in mitochondrial superoxide in rat brain. Our findings demonstrate that OLZ and ARI do not induce oxidative damage in rat brain as observed after HAL and CLO treatment.
Assuntos
Antipsicóticos/toxicidade , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Haloperidol/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Animais , Aripiprazol , Benzodiazepinas/toxicidade , Clozapina/toxicidade , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Olanzapina , Piperazinas/toxicidade , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Quinolonas/toxicidade , Ratos , Ratos Wistar , Superóxidos/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
Memantine is a non-competitive N-methyl-d-aspartate receptor antagonist, which has been employed in the clinic as a neuroprotective agent for the treatment of several dementias, particularly Alzheimer's disease. In this study, we evaluated pharmacological effects of the acute administration of memantine on memory process. Memory retention scores were evaluated in normal adult Wistar rats injected with saline and memantine (2, 5, 10, and 20 mg/kg, IP) and then subjected to the step-down inhibitory avoidance task, habitation to an open-field apparatus, and object recognition task. The treatment with higher doses of memantine (10 and 20 mg/kg) injected 60 min before or immediately after training-session impaired acquisition and retention of aversive memory in the inhibitory avoidance task. In addition, higher doses of memantine injected 60 min before the first open-field exposure also impaired habituation during the second exposure to the apparatus. No significant differences were observed in the performance of rats treated with memantine, in all doses tested, compared to saline-treated rats in the object recognition task. Notably, we observed that at 5 mg/kg, memantine increased spontaneous locomotion and exploration in the rat open-field test. In conclusion, present findings support the view that memantine at lower doses did not affect memory formation in normal rats, but at high doses memantine, induce hyperlocomotion, which could bias the interpretation of the animal behavior assessed in memory tests.
Assuntos
Antagonistas de Aminoácidos Excitatórios/farmacologia , Memantina/farmacologia , Memória/efeitos dos fármacos , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Comportamento Exploratório/efeitos dos fármacos , Habituação Psicofisiológica/efeitos dos fármacos , Injeções Intraperitoneais , Masculino , Memantina/administração & dosagem , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Wistar , Reconhecimento Psicológico/efeitos dos fármacosRESUMO
Bipolar disorder (BD) is thought to be associated with abnormalities within discrete brain regions associated with emotional regulation, particularly in fronto-limbic-subcortical circuits. Several reviews have addressed the involvement of the prefrontal cortex in the pathophysiology of BD, whereas little attention has been given to the role of the hippocampus. This study critically reviews data from brain imaging, postmortem, neuropsychological, and preclinical studies, which suggested hippocampal abnormalities in BD. Most of the structural brain imaging studies did not find changes in hippocampal volume in BD, although a few studies suggested that anatomical changes might be restricted to the psychotic, pediatric, or unmedicated BD subgroups. Functional imaging studies showed abnormal brain activation in the hippocampus and its closely related regions during emotional, attentional, and memory tasks. This is consistent with neuropsychological findings that revealed a wide range of cognitive disturbances during acute mood episodes and a significant impairment in declarative memory during remission. Postmortem studies indicate abnormal glutamate and GABA transmission in the hippocampus of BD patients, whereas data from preclinical studies suggest that the regulation of hippocampal plasticity and survival might be associated with the therapeutic effects of mood stabilizers. In conclusion, the available evidence suggests that the hippocampus plays an important role in the pathophysiology of BD.
Assuntos
Transtorno Bipolar/fisiopatologia , Hipocampo/fisiopatologia , Animais , Antimaníacos/farmacologia , Modelos Animais de Doenças , Ácido Glutâmico/metabolismo , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Plasticidade Neuronal , Cintilografia , Ácido gama-Aminobutírico/metabolismoRESUMO
Malathion [S-(1,2-dicarbethoxy) ethyl-0,0-dimethyl-phosphorodithioate] is an organophosphorus compound that is widely used as pesticide especially in developing countries. This pesticide affects the central nervous system by inhibiting acetylcholinesterase, leading to an increase of acetylcholine in the synaptic cleft, and subsequent activation of cholinergic muscarinic and nicotinic receptors. In humans, intoxication with organophosphates causes a wide range of neurological symptoms, including memory deficits. The present study was aimed to investigate the effects of the acute (1 h prior the test) and subacute (once a day for 28 days) exposure to malathion at doses of 25, 50, 100 and 150 mg/kg in rats tested in the step-down inhibitory avoidance task, open-field habituation and elevated plus-maze tests. Interestingly, the acute and subacute treatment with malathion impaired aversive-memory in the step-down inhibitory avoidance task, but did not alter the animal performance in the elevated plus-maze and in the habituation to the open-field tests, and neither modified spontaneous locomotion. The activity of acetylcholinesterase enzyme was significantly reduced after subacute, but not acute, treatment with malathion (25, 100 and 150 mg/kg). Our results suggest that malathion impairs aversive-memory retention but not non-associative memory, without affecting anxiety-related behaviors. These findings support the view that the inhibition of acetylcholinesterase enzyme is not correlated with cognitive deficits observed in acute and subacute malathion-treated rats.