Quantifying the 5-HT1 agonist action of buspirone in man

Rationale: Buspirone is used as a neuroendocrine challenge in which the inc rease of circulating prolactin is taken as a measure of the sensitivity of central serotonergic (5-HT1A) pathways. Interpretation of the test is compl icated, however, by the fact that buspirone possesses D-2 antagonist and 5- HT1A agonist activity, both of which will result in the release of prolacti n. To understand the significance of prolactin secretion in response to bus pirone, it is important to measure the differential actions of the two cont rolling pathways. Objective: To characterise the dual action of buspirone i n stimulating the secretion of prolactin by blocking the 5-HT1A action with the 5-HT1A antagonist action of pindolol. Methods: Healthy male subjects ( n=35) received buspirone (0.5 mg.kg bw(-1) orally) with and without pre-tre atment with the 5-HT1A receptor antagonist pindolol (40 mg over 2 days, 0.5 mg.kg bw(-1) on test day). Nine subjects underwent two additional trials i n which they received a placebo with and without pre-treatment with pindolo l. Results: Pindolol alone caused a small but significant reduction (18%) i n the tonic release of prolactin. Buspirone alone produced a robust prolact in response which was reduced to approximately half by pindolol pre-treatme nt. Pindolol pre-treatment also, on average, delayed the onset and peak of the prolactin response. There was wide variation among individuals both in the absolute response to buspirone and in the proportion that could be attr ibuted to the non-serotonergic agonist action of buspirone (22-82% IQ range ). Conclusions: Our results indicate that while serotonergic pathways play a minor role in the tonic release of prolactin, the response to a buspirone challenge alone cannot be used as a simple index of central serotonergic a ctivity. However, if two challenges are carried out, one with buspirone and the other with buspirone plus pindolol, quantitative measures can be made of the sensitivity of both the 5-HT1A and the putative D-2 pathways control ling prolactin release.