Buspirone challenge: preliminary evidence for a role for central 5-HT1a receptor function in impulsive aggressive behavior in humans.

The prolactin (PRL) response to challenge with buspirone hydrochloride, a serotonin1a (5-HT1a) receptor agonist, was examined in 5 healthy male volunteers and in 10 healthy male and female patients with primary DSM-III personality disorder. In healthy volunteers, pretreatment with the nonselective 5-HT receptor antagonist, metergoline (4 mg p.o.) completely suppressed the maximal PRL response to buspirone challenge. Pretreatment with the nonselective beta-adrenergic/5-HT1-like antagonist, pindolol suppressed the maximal PRL response to buspirone challenge depending upon dose (i.e., between 49 to 90% suppression at best dose). In personality disorder patients, PRL responses to buspirone challenge correlated inversely with self-assessed "irritability" (r = -.76, n = 10, p less than .01). These data suggest that the PRL response to buspirone challenge reflects the responsivity of 5-HT1a receptors in the limbic-hypothalamus in humans and that reduced sensitivity of these receptors is associated with an important component of impulsive aggressive behaviors in personality disorder patients.