Putative mechanisms of buspirone-induced antinociception in the rat.
Intraperitoneal administration of the serotonin 5-HT1A agonist, buspirone (1-5 mg/kg), produced dose- and time-related core hypothermia that was coincident with analgesia against a thermally noxious stimulus. Surface body temperature was not altered by buspirone. The 5-HT1A antagonist, NAN-190 (2 mg/kg, s.c.), blocked both hypothermic and analgesic effects, while systemic administration of the opioid antagonist, naloxone (1 mg/kg, s.c.), did not change the pattern of buspirone-induced hypothermia or analgesia. The apparent lack of opioid involvement and the documented role of the 5-HT1A receptor system in neuroendocrine substrates of thermoregulation and pain modulation prompted study of adrenal function in these buspirone-induced effects. Buspirone (5 mg/kg, i.p.) produced significant elevations in plasma epinephrine (EPI) and corticosterone (CST). Bilateral adrenalectomy reduced both control and buspirone-elevated EPI and CST levels and attenuated the antinociceptive, but not hypothermic, effects of buspirone (1-5 mg/kg, i.p.). Administration of the phenylethanolamine-N-methyltransferase (PNMT) inhibitor, dichloromethylbenzylamine (DCMB: 25 mg/kg, i.p.) reduced basal and buspirone-elevated plasma EPI, but not CST levels. This treatment did not affect buspirone-induced hypothermia, while significantly reducing buspirone antinociception. Pretreatment with the CST synthesis inhibitor, aminoglutethemide (AG: 2 x 25 mg/kg, i.p.), reduced plasma CST levels while not significantly affecting EPI. AG pretreatment did not alter the hypothermic effects of buspirone, but attenuated antinociception produced by the highest buspirone dose. The AG-induced reductions of buspirone antinociception were less than those effects produced by DCMB treatment. These data suggest that buspirone-induced antinociception may be a non-opioid, adrenally mediated co- and/or epi-phenomenon to core hypothermia evoked by 5-HT1A receptor agonism.
Giordano
James
J
Neuropharmacology Laboratory, College of Pharmacy and Health Sciences, Drake University, Des Moines, IA, USA Medical Service Corps, United States Navy, Fleet Hospital, Des Moines, IA, USA.
Rogers
LaVerne
L
D000315:Adrenalectomy; D000616:Aminoglutethimide / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D002065:Buspirone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007035:Hypothermia / Q000139:chemically induced; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012702:Serotonin Antagonists / Q000494:pharmacology; D013997:Time Factors
D000700:Analgesics; D001596:Benzylamines; D010879:Piperazines; D012702:Serotonin Antagonists; D000616:Aminoglutethimide; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; D009270:Naloxone; D002065:Buspirone