Effect of Ketoconazole on Early Maternal Separation Stress Model in Rats: A Neurobehavioral and Biochemical Approach

Abstract

Adverse early life events, such as early maternal separation, may alter the normal pattern of brain development and subsequently the vulnerability to a variety of mental disorders in adulthood. Maternal separation relatively changes behavioral and biochemical responses leading to an overactivation of the hypothalamic-pituitary-adrenal (HPA) axis, and subsequently increases the ACTH level. In this study, we aimed to evaluate the role of a corticosteroid blocker, ketoconazole, in behavioral, hematological and biochemical changes in rat underwent maternal separation (MS). For this purpose, On postnatal days 1-7, rats were submitted daily to MS for 1h30min per day. At 3 months of age, rats were given a high dose of ketoconazole (200mg/kg), exploratory activity and anxiety-like behavior were evaluated using the open field test and elevated plus maze test, olfactory-like behavior was evaluated using the olfactory recogneting and biochemical and hematological profiles were also evaluated. We found that MS provoked depressive and anxiety-like behaviors, olfactory sensibility and biochemical changes (increase in level of blood glucose and ACTH) in adult rat. In addition, treatment of stressed rat by ketoconazole could modulate the above-mentioned negative effects of maternal separation"MS". In conclusion, our results demonstrated that ketoconazole decrease anxiety like behavior and regulate biochemical change induced by maternal separation stress.

Study of Plasma Corticosterone Upon Chronic Stress Induction and Its Effect on Follicular Development in Rattus norvegicus

“…This lower corticosterone response may be attributed to the change in response of HPA axis to ACTH [15]. To study the effect of stress-induced corticosterone elevation on the follicular development and PCOS induction, corticosterone inhibitor, ketoconazole was administered to suppress the 17α-hydroxylase activity, 11β-hydroxylase activity and thereby reducing the production of the primary stress hormone [16][17][18]. The inclusion of ketoconazole in the study proved to be effective as the stressed animals dosed with 50 mg/kg body weight ketoconazole showed similar corticosterone values in the plasma of control animals (Fig.…”