Prenatal Olanzapine Induced Behavioural Changes in Swiss Albino Mice

Abstract

Soumya Khanna1 , Gunjan Rai2 , Anand Mishra3

BACKGROUND Olanzapine is an atypical antipsychotic agent and is one of the most commonly used drugs for episodes of psychosis. Women with psychosis and on medications for the condition may become pregnant. The safety profile of olanzapine has not yet been completely established during pregnancy. We wanted to study the behavioural changes in pups of swiss albino mice who received Olanzapine during gestational period. METHODS The study was performed in the Department of Anatomy, Institute of Medical Sciences, Banaras Hindu University, Varanasi. Thirty adult female Swiss albino mice of weight 20 - 25 gms and average age of 80 - 100 days, were utilized after approval of institutional ethical committee. The temperature of animal room was kept ambient and relative humidity of 50 - 60% was maintained with 12 hr of light and 12 hr of dark cycle. In the evening the female mice who were in their preestrous phase were transferred to the cages containing male mice in ratio of 2:1. In the morning the pregnancy was checked for by the presence of vaginal plug and was designated as day zero of gestation. All pregnant mice were divided into three equal groups of 10 mice each. Group 1 was treated with Olanzapine at dose 2 mg/Kg orally throughout gestation period. Group 2 was treated with Olanzapine at dose 6 mg/Kg orally throughout gestation period. Group 3 was given equal amount of tap water at the same time via the same route. Animals from all the three groups were allowed to deliver. The delivered pups of the three groups were subjected to behavioural tests namely open field test, elevated plus maze test, and Morris water maze test, at the age of 8 weeks approximately to measure exploratory, anxiety, memory and learning behaviour. RESULTS Olanzapine treated mice for the dose 2 mg/Kg showed heightened activity and reduced anxiety in open field and elevated plus maze test as compared to control. However, for dose 6 mg/Kg the offspring showed heightened anxiety and fearfulness as compared to controls. The low dose group had improved memory and learning behaviour whereas in high dose it was distorted. CONCLUSIONS Above findings suggest that Olanzapine has a deleterious effect on nervous system development when given in high doses, thus resulting in abnormal anxiety states, possibly due to its potent activity at dopamine, serotonin, muscarinic, histamine and adrenergic receptors.

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