Selective serotonin reuptake inhibitors and neuroendocrine function

Selective serotonin (5-HT) reuptake inhibitors (SSRIs) are effective drugs for the treatment of several neuropsychiatric disorders associated with red uced serotonergic function. Serotonergic neurons play an important role in the regulation of neuroendocrine function. This review will discuss the acu te and chronic effects of SSRIs on neuroendocrine function. Acute administr ation of SSRIs increases the secretion of several hormones, but chronic tre atment with SSRIs does not alter basal blood levels of hormones. However, a daptive changes are induced by long-term treatment with SSRIs in serotonerg ic, noradrenergic and peptidergic neural function. These adaptive changes, particularly in the function of specific post-synaptic receptor systems, ca n be examined from altered adrenocorticotrophic hormone (ACTH), cortisol, o xytocin, vasopressin, prolactin, growth hormone (GH) and renin responses to challenges with specific agonists. Neuroendocrine challenge tests both in experimental animals and in humans indicate that chronic SSRIs produce an i ncrease in serotonergic terminal function, accompanied by desensitization o f post-synaptic 5-HT1A receptor-mediated ACTH, cortisol, GH and oxytocin re sponses, and by supersensitivity of post-synaptic 5-HT2A (and/or 5-HT2C) re ceptor-mediated secretion of hormones. Chronic exposure to SSRIs does not a lter the neuroendocrine stress-response and produces inconsistent changes i n alpha(2) adrenoceptor-mediated GH secretion. Overall, the effects of SSRI s on neuroendocrine function are dependent on adaptive changes in specific neurotransmitter systems that regulate the secretion of specific hormones.