Micro1-opioid antagonist naloxonazine alters ethanol discrimination and consumption.
The endogenous opioid system is implicated in excessive ethanol-drinking behavior. However, the role of individual opioid receptor subtypes in the mechanism underlying excessive ethanol-drinking behavior is not yet well understood. Therefore, we investigated the ability of a selective micro1-opioid antagonist, naloxonazine, to modulate ethanol-drinking behavior and ethanol discrimination in a rat model with the use of ethanol self-administration and drug discrimination paradigms. The effects of naloxonazine (0.001-10 mg/kg) on ethanol intake were examined in Sprague-Dawley rats under conditions of limited access to 10% (wt./vol.) ethanol and ad libitum access to food and water. Pretreatment with high doses of naloxonazine (1-10 mg/kg) significantly reduced ethanol consumption. When the effects of naloxonazine on food intake in free-feeding male rats were examined, naloxonazine (1.8-10 mg/kg) significantly suppressed 24-h food intake. Another group of rats was trained to discriminate ethanol (1.25 g/kg, i.p.) from saline on a fixed-ratio schedule (FR 10), and ethanol dose-response tests were conducted once rats had acquired ethanol-saline discrimination. Injections were given 15 min before ethanol dose-response tests were conducted, and after characterization of the ethanol dose-response curve, the effects of naloxonazine on ethanol discrimination were assessed by administering naloxonazine (0.001-10 mg/kg, i.p.) 15 min before ethanol administration. Treatment with naloxonazine (0.001-1.8 mg/kg, i.p.) before the ED(100) dose of ethanol partially antagonized the discriminative stimulus of ethanol without having any effect on the response rate. The results support the suggestion of involvement of micro1-opioid receptors in the discriminative effects of ethanol and ethanol-drinking behavior.
Mhatre
Molina
M
Free Radical Biology and Aging, Oklahoma Medical Research Foundation, 825 N.W. 13th Street, Oklahoma City, OK 73190-3000, USA.
Holloway
Frank
F
D000428:Alcohol Drinking / Q000523:psychology*; D000818:Animals; D002492:Central Nervous System Depressants / Q000097:blood; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D000431:Ethanol / Q000097:blood; D008297:Male; D009270:Naloxone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors*
D002492:Central Nervous System Depressants; D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; D009270:Naloxone; D000431:Ethanol; C034643:naloxonazine