Naloxone-induced hypoalgesia: lack of involvement of the GABA-benzodiazepine receptor complex.
Previous evidence has demonstrated that repeated daily administration of the opiate receptor antagonist naloxone prior to assessment of pain sensitivity provokes the development of a nonopioid form of hypoalgesia. The present experiments assessed whether the GABA-benzodiazepine receptor complex may be involved in the mediation of this effect. Male Wistar rats were administered 10 mg/kg naloxone prior to hot-plate tests (48.5 degrees C) for pain sensitivity for 8 consecutive days. Control animals were administered saline prior to, and naloxone 2-4 h after, assessment of pain reactivity. Beginning on the fourth or fifth day of this regimen, animals tested under the influence of naloxone displayed longer paw-lick latencies than controls. Preadministration of the GABAA agonist muscimol (1.0-5.0 mg/kg) and GABAA antagonist bicuculline (0.25-1.0 mg/kg) failed to affect paw-lick latencies in naloxone-tested and control rats. The GABAB receptor agonist baclofen (1.0-5.0 mg/kg) and the benzodiazepine receptor agonist diazepam (1.0-5.0 mg/kg) both elevated paw-lick latencies to the same degree in both groups of animals. These results suggest that the GABA-benzodiazepine receptor complex is not involved in the mediation of naloxone-induced hypoalgesia.
Rochford
J
J
Department of Psychology, Concordia University, Montreal, Quebec, Canada.
Stewart
J
J
D000698:Analgesia; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*
D011963:Receptors, GABA-A; D009118:Muscimol; D009270:Naloxone; D001418:Baclofen; D003975:Diazepam; D001640:Bicuculline