NEUROENDOCRINE RESPONSES TO SEROTONERGIC AGONISTS AS INDEXES OF THE FUNCTIONAL STATUS OF CENTRAL SEROTONIN NEUROTRANSMISSION IN HUMANS - A PRELIMINARY COMPARATIVE-ANALYSIS OF NEUROENDOCRINE END-POINTS VERSUS OTHER END-POINT MEASURES

The status of central serotonergic neurotransmission and of specific s erotonin (5-HT) receptor subtype sensitivity has been inferred from ne uroendocrine and other endpoint responses to serotonergic agents given to humans. The question of whether changes in neuroendocrine responsi vity to the 5-HT2C partial agonist, meta-chlorophenylpiperazine (m-CPP ), are accompanied by similar changes in other endpoints (temperature, behavior) is addressed in this brief review of published studies. The se studies were selected based on the following criteria: (1) neuroend ocrine (cortisol, prolactin increases) and at least one other endpoint (behavior and/or temperature increases) were measured in the same pop ulations, and (2) statistically significant changes were observed afte r m-CPP in the healthy volunteer control or pre-long-term-treatment su bjects. Parenthetically, in the 13 of 14 studies that reported both pr olactin and cortisol responses, the results were congruent for the two neuroendocrine measures in 12 of the 13 (92%). However, neuroendocrin e versus behavioral results were in agreement in fewer (7 of the 13) s tudies (54%). Neuroendocrine vs. temperature results were non-concorda nt in all 4 of the studies which included temperature measurements. Th ese generally disparate findings suggest that these different endpoint s may reflect brain serotonin neuroanatomic and receptor subsystem com plexity and/or m-CPP's complex pharmacological properties. Thus, these neuroendocrine response measures cannot at this time be considered a general index of the other response measures, nor necessarily an index of the functional status of central serotonergic neurotransmission un til this is established by more direct experimental investigations.