The preventive effects of ascorbic acid supplementation on locomotor and acetylcholinesterase activity in an animal model of schizophrenia induced by ketamine

ABSTRACT Studies have shown that schizophrenic patients seem to have nutritional deficiencies. Ascorbic acid (AA) has an important antioxidant effect and neuromodulatory properties. The aim of this study was to evaluate the effects of AA on locomotor activity and the acetylcholinesterase activity (AChE) in an animal model of schizophrenia (SZ). Rats were supplemented with AA (0.1, 1, or 10 mg/kg), or water for 14 days (gavage). Between the 9th and 15th days, the animals received Ketamine (Ket) (25 mg/kg) or saline (i.p). After the last administration (30 min) rats were subjected to the behavioral test. Brain structures were dissected for biochemical analysis. There was a significant increase in the locomotor activity in Ket treated. AA prevented the hyperlocomotion induced by ket. Ket also showed an increase of AChE activity within the prefrontal cortex and striatum prevented by AA. Our data indicates an effect for AA in preventing alterations induced by Ket in an animal model of SZ, suggesting that it may be an adjuvant approach for the development of new therapeutic strategies within this psychiatric disorder.

Ketamine alters behavior and decreases BDNF levels in the rat brain as a function of time after drug administration

Objective: To evaluate behavioral changes and brain-derived neurotrophic factor (BDNF) levels in rats subjected to ketamine administration (25 mg/kg) for 7 days. Method: Behavioral evaluation was undertaken at 1 and 6 hours after the last injection. Results: We observed hyperlocomotion 1 hour after the last injection and a decrease in locomotion after 6 hours. Immobility time was decreased and climbing time was increased 6 hours after the last injection. BDNF levels were decreased in the prefrontal cortex and amygdala when rats were killed 6 hours after the last injection, compared to the saline group and to rats killed 1 hour after the last injection. BDNF levels in the striatum were decreased in rats killed 6 hours after the last ketamine injection, and BDNF levels in the hippocampus were decreased in the groups that were killed 1 and 6 hours after the last injection. Conclusion: These results suggest that the effects of ketamine on behavior and BDNF levels are related to the time at which they were evaluated after administration of the drug. .

Energy metabolism, leptin, and biochemical parameters are altered in rats subjected to the chronic administration of olanzapine / Metabolismo calórico, leptina e parâmetros bioquímicos se alteram em ratos submetidos à administração crônica de olanzapina

OBJECTIVES: Olanzapine, an atypical antipsychotic drug with affinities for dopamine, serotonin, and histamine binding sites appears to be associated with substantial weight gain and metabolic alterations. The aim of this study was to evaluate weight gain and metabolic alterations in rats treated with olanzapine on a hypercaloric diet. METHODS: We used 40 rats divided into 4 groups: Group 1, standard food and water conditions (control); Group 2, standard diet plus olanzapine; Group 3, cafeteria diet (hypercaloric); and Group 4, olanzapine plus cafeteria diet. Olanzapine was administered by gavage at a dose of 3 mg/kg for 9 weeks. RESULTS There were no significant changes in the cholesterol levels in any group. Glucose levels increased in Group 3 by the fourth week. Triglyceride levels were altered in group 2 toward the end of the experiment. Leptin levels decreased in Groups 2 and 4. Complex II activity in the muscles and liver was altered in Group 2 (muscle), and Groups 2, 3, and 4 (liver). Complex IV activity was altered only in the liver in Group 2, without significant alterations within the muscles. CONCLUSION: These results suggest that olanzapine is correlated with weight gain and the risks associated with obesity.

OBJETIVOS: A olanzapina, uma droga antipsicótica atípica com afinidade por locais de ligação de dopamina, serotonina e histamina, parece se associar a um ganho de peso e a alterações metabólicas consideráveis. O objetivo desse estudo foi avaliar o ganho de peso e as alterações metabólicas em ratos tratados com olanzapina numa dieta hipercalórica. MÉTODOS: Usamos 40 ratos divididos em 4 grupos: Grupo 1, condições padrão de alimento e água (controle); Grupo 2, dieta padrão mais olanzapina; Grupo 3, dieta hipercalórica; e Grupo 4, olanzapina mais dieta hipercalórica. Olanzapina foi administrada por gavagem a uma dose de 3 mg/kg por 9 semanas. RESULTADOS: Não houve alterações significativas nos níveis de colesterol em qualquer um dos grupos. Os níveis de glicose aumentaram no Grupo 3 por volta da quarta semana. Os níveis de triglicerídeos estavam alterados no Grupo 2 ao final do experimento. Os níveis de leptina diminuíram nos Grupos 2 e 4. A atividade do complexo II nos músculos e no fígado se alterou no Grupo 2 (músculos) e nos Grupos 2, 3 e 4 (fígado). A atividade do complexo IV se alterou apenas no fígado no Grupo 2, sem alterações significativas nos músculos. CONCLUSÃO: Esses resultados sugerem que olanzapina se correlaciona ao ganho de peso e aos riscos associados à obesidade.

Effect of acute administration of ketamine and imipramine on creatine kinase activity in the brain of rats / Efeito da administração aguda da cetamina e imipramina sobre a atividade da creatina quinase no encéfalo de ratos

OBJECTIVE: Clinical findings suggest that ketamine may be used for the treatment of major depression. The present study aimed to compare behavioral effects and brain Creatine kinase activity in specific brain regions after administration of ketamine and imipramine in rats. METHOD: Rats were acutely given ketamine or imipramine and antidepressant-like activity was assessed by the forced swimming test; Creatine kinase activity was measured in different regions of the brain. RESULTS: The results showed that ketamine (10 and 15mg/kg) and imipramine (20 and 30mg/kg) reduced immobility time when compared to saline group. We also observed that ketamine (10 and 15mg/kg) and imipramine (20 and 30mg/kg) increased Creatine kinase activity in striatum and cerebral cortex. Ketamine at the highest dose (15mg/kg) and imipramine (20 and 30mg/kg) increased Creatine kinase activity in cerebellum and prefrontal cortex. On the other hand, hippocampus was not affected. CONCLUSION: Considering that metabolism impairment is probably involved in the pathophysiology of depressive disorders, the modulation of energy metabolism (like increase in Creatine kinase activity) by antidepressants could be an important mechanism of action of these drugs.

OBJETIVO: Vários achados clínicos sugerem que a cetamina apresenta efeito antidepressivo. O presente estudo tem como objetivo comparar efeitos comportamentais e a atividade da creatina quinase em regiões específicas do encéfalo após a administração de cetamina e imipramina em ratos. MÉTODO: Ratos Wistar receberam uma administração aguda de cetamina ou imipramina e a atividade antidepressiva foi avaliada pelo teste de nado forçado; a atividade da creatina quinase foi medida em diferentes regiões encefálicas. RESULTADOS: Os resultados mostraram que a cetamina (10 e 15mg/kg) e a imipramina (20 e 30mg/kg) diminuíram o tempo de imobilidade quando comparados ao grupo salina. Também foi observado que a cetamina (10 e 15mg/kg) e a imipramina (20 e 30mg/kg) aumentaram a atividade da creatina quinase no estriado e córtex cerebral. A dose mais alta de cetamina (15mg/kg) e a imipramina (20 e 30mg/kg) aumentaram a atividade da creatina quinase no cerebelo e córtex pré-frontal. Por outro lado, o hipocampo não foi alterado. CONCLUSÃO: Considerando que a diminuição no metabolismo provavelmente está envolvida na fisiopatologia da depressão, a modulação do metabolismo energético (como um aumento na atividade da creatina quinase) por antidepressivos pode ser um importante mecanismo de ação destes fármacos.