Endocrinological and behavioral effects of chronic fluxilan administration in rats

Abstract

Chronic stress induces changes in the neuroendocrine and neuronal system, including elevation of catecholamines and corticosterone (CORT) levels, and could be an important factor in initial depression. Antidepressants affect monoaminergic neurotransmission and modulate central neuropeptides involved in the coordination of stress response and the control of HPA axis activity. We studied the effects of chronic treatment with fluxilan, a selective inhibitor of serotonin reuptake, in unstressed controls and chronic unpredictable mild stress (CUMS) rats, on behaviour and plasma noradrenaline (NA), adrenaline (A), corticosterone (CORT) and adrenocorticotropic hormone (ACTH). CUMS did not affect plasma NA, A and ACTH, but elevated plasma CORT content. Plasma concentration of catecholamines after fluxilan administration was significantly increased in control and CUMS group. On the other hand, fluxilan expressed no effect on plasma ACTH and CORT concentrations in control animals, but decreased ACTH and CORT levels in CUMS animals. behaviorally, fluxilan treated animals displayed enhanced anxiety. The results demonstrate that the anxiogenic effects of chronic fluxilan administration are similar to those reported by many other studies. The findings described here suggest that elevated plasma catecholamines may contribute to an adverse effect of this drug on cardiovascular parameters during antidepressant therapy.

Keywords

• depression
• catecholamines
• corticosterone
• adrenocorticotropic hormone
• antidepressant