Neuroendocrine responses to serotonergic agonists as indices of the functional status of central serotonin neurotransmission in humans: a preliminary comparative analysis of neuroendocrine endpoints versus other endpoint measures.

The status of central serotonergic neurotransmission and of specific serotonin (5-HT) receptor subtype sensitivity has been inferred from neuroendocrine and other endpoint responses to serotonergic agents given to humans. The question of whether changes in neuroendocrine responsivity 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. These studies were selected based on the following criteria: (1) neuroendocrine (cortisol, prolactin increases) and at least one other endpoint (behavior and/or temperature increases) were measured in the same populations, and (2) statistically significant changes were observed after m-CPP in the healthy volunteer control or pre-long-term-treatment subjects. Parenthetically, in the 13 of 14 studies that reported both prolactin and cortisol responses, the results were congruent for the two neuroendocrine measures in 12 of the 13 (92%). However, neuroendocrine versus behavioral results were in agreement in fewer (7 of the 13) studies (54%). Neuroendocrine vs. temperature results were non-concordant in all 4 of the studies which included temperature measurements. These generally disparate findings suggest that these different endpoints may reflect brain serotonin neuroanatomic and receptor subsystem complexity 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 until this is established by more direct experimental investigations.