Effects of naltrexone, duloxetine, and a corticotropin-releasing factor type 1 receptor antagonist on binge-like alcohol drinking in rats.
A 'binge' is defined by National Institute on Alcohol Abuse and Alcoholism as an excessive pattern of alcohol drinking that produces blood-alcohol levels (BALs) greater than 0.08 g% within a 2-h period and may or may not be associated with dependence. The purpose of this investigation was to explore the effects of several neuropharmacological agents in an animal model in which outbred rats voluntarily and orally self-administer pharmacologically meaningful alcohol doses that produce BALs >or=0.08 g% in daily limited access two-bottle choice and operant drinking sessions. Rats were trained to self-administer either 10% (w/v) alcohol solution sweetened with 'supersac' (3% glucose+0.125% saccharin) or supersac alone versus water in a two-bottle choice or operant situation during 30-min daily sessions. Rats were then injected systemically with multiple doses of duloxetine, naltrexone, and the corticotropin-releasing factor antagonist, MPZP, in Latin-square designs. Alcohol binge drinkers reliably consumed amounts of alcohol sufficient to produce BALs >or=0.08 g%. Duloxetine dose-dependently suppressed two-bottle choice alcohol binge drinking and operant alcohol responding as well as operant supersac responding, but did not affect two-bottle choice supersac drinking. Naltrexone-suppressed alcohol binge drinking at very low doses and suppressed supersac drinking at moderate-to-high doses. MPZP did not affect alcohol or supersac consumption. Different profiles for drugs that suppress binge-like alcohol drinking compared with dependence-induced drinking provide a heuristic foundation for future medications development.
Ji
Dong
D
Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, California, USA.
Gilpin
Nicholas W
NW
Richardson
Heather N
HN
Rivier
Catherine L
CL
Koob
George F
GF
D000427:Alcohol Deterrents / Q000494:pharmacology*; D000818:Animals; D016739:Behavior, Addictive / Q000517:prevention & control / Q000523:psychology; D003216:Conditioning, Operant / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000068736:Duloxetine Hydrochloride; D000431:Ethanol / Q000097:blood / Q000506:poisoning*; D008297:Male; D009271:Naltrexone / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D012439:Saccharin / Q000494:pharmacology; D012646:Self Administration; D013549:Sweetening Agents / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology*; D000099052:CRF Receptor, Type 1
D000427:Alcohol Deterrents; C528552:N,N-bis(2-methoxyethyl)-3-(4-methoxy-2-methylphenyl)-2,5-dimethyl-pyrazolo(1,5-a)pyrimidin-7-amine; D011743:Pyrimidines; D018019:Receptors, Corticotropin-Releasing Hormone; D013549:Sweetening Agents; D013876:Thiophenes; D000431:Ethanol; D000099052:CRF Receptor, Type 1; D009271:Naltrexone; D000068736:Duloxetine Hydrochloride; D012439:Saccharin