Attenuation of morphine withdrawal signs by the GABA(B) receptor agonist baclofen.
The present study examined the effect of the gamma-aminobutyric acidB (GABA(B)) receptor agonist, baclofen on naloxone-induced withdrawal signs in morphine-dependent rats and modification by the antagonist, 3-aminopropyl-cyclohexylmethylphosphinic acid (CGP 46381). Morphine was administered via mini-osmotic pumps for 7 days to induce physical dependence. Baclofen (20 mg kg(-1)) decreased stereotyped head movements, chewing, chatter, ptosis and body weight loss, induced by naloxone (10 mg kg(-1)) in morphine-dependent rats. CGP 46381 (20 mg kg(-1)) reversed the effects exerted by baclofen on stereotyped head movements, ptosis, and weight loss and partially reversed the effect of baclofen on chewing. It can be concluded that baclofen has some potential in the treatment of opioid withdrawal and that GABA(B) receptors may be implicated in such a withdrawal.
Bexis
S
S
Department of Anaesthesia and Intensive Care, The University of Adelaide, South Australia, Australia.
Ong
J
J
White
J
J
D000818:Animals; D001418:Baclofen / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D004336:Drug Antagonism; D004338:Drug Combinations; D018755:GABA Agonists / Q000627:therapeutic use*; D018756:GABA Antagonists / Q000494:pharmacology; D008297:Male; D009021:Morphine Dependence / Q000188:drug therapy*; D009270:Naloxone / Q000494:pharmacology; D010721:Phosphinic Acids / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*
D004338:Drug Combinations; D018755:GABA Agonists; D018756:GABA Antagonists; D010721:Phosphinic Acids; C086109:3-aminopropyl-cyclohexylmethylphosphinic acid; D009270:Naloxone; D001418:Baclofen