Effects of chronic administration of imipramine on the hyperactivity of hypothalamic-pituitary-adrenal axis in neonatal clomipramine treated rats

Objective: To study the effects of chronic administration of imipramine on the hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis in neonatal clomipramine model of depression. Methods: Male rat pups were given clomipramine (15 mg/kg, s.c., twice daily) or equivolume of saline from the time they were five days old and until they were twenty-one days old. At three months of age, clomipramine treated rats were administered either imipramine (20 mg/kg, s.c.,) or saline once daily for 14 days. Serum corticosterone level was estimated before and after dexamethasone (100 μg/kg, s.c.,) administration in all animals. Results: Data indicated an enhanced baseline corticosterone level and nonsuppression to dexamethasone in clomipramine treated rats. The levels of corticosterone was reduced to the levels of control group in rats subjected to 14 days of imipramine treatment. Conclusion: Neonatal treatment of clomipramine produced dysregulation of HPA axis, and this neuroendocrine abnormality was reversed with chronic administration of imipramine.