title: Quantifying the 5-HT1A agonist action of buspirone in man.
abstract: BACKGROUND
  Buspirone is used as a neuroendocrine challenge in which the increase of circulating prolactin is taken as a measure of the sensitivity of central serotonergic (5-HT(1A)) pathways. Interpretation of the test is complicated, however, by the fact that buspirone possesses D(2) antagonist and 5-HT(1A) agonist activity, both of which will result in the release of prolactin. To understand the significance of prolactin secretion in response to buspirone, it is important to measure the differential actions of the two controlling pathways.
  
  
  OBJECTIVE
  To characterise the dual action of buspirone in stimulating the secretion of prolactin by blocking the 5-HT(1A) action with the 5-HT1A antagonist action of pindolol.
  
  
  METHODS
  Healthy male subjects (n=35) received buspirone (0.5 mg x kg bw(-1) orally) with and without pre-treatment with the 5-HT(1A) receptor antagonist pindolol (40 mg over 2 days, 0.5 mg x kg bw(-1) on test day). Nine subjects underwent two additional trials in which they received a placebo with and without pre-treatment with pindolol.
  
  
  RESULTS
  Pindolol alone caused a small but significant reduction (18%) in the tonic release of prolactin. Buspirone alone produced a robust prolactin response which was reduced to approximately half by pindolol pre-treatment. 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 attributed 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 activity. 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-HT(1A) and the putative D(2) pathways controlling prolactin release.
authors.affiliation: School of Sport and Exercise Sciences, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. m.w.bridge@bham.ac.uk
authors.forename: M W
authors.initials: MW
authors.lastname: Bridge
authors.forename: G
authors.initials: G
authors.lastname: Marvin
authors.forename: C E
authors.initials: CE
authors.lastname: Thompson
authors.forename: A
authors.initials: A
authors.lastname: Sharma
authors.forename: D A
authors.initials: DA
authors.lastname: Jones
authors.forename: M J
authors.initials: MJ
authors.lastname: Kendall
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D002065:Buspirone / Q000494:pharmacology*; D018592:Cross-Over Studies; D006801:Humans; D008297:Male; D010869:Pindolol / Q000494:pharmacology; D011388:Prolactin / Q000378:metabolism; D011985:Receptors, Serotonin / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D016037:Single-Blind Method; D018709:Statistics, Nonparametric
chemical_list: D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D011388:Prolactin; D010869:Pindolol; D002065:Buspirone