Memantine enhances the inhibitory effects of naltrexone on ethanol consumption.
Effects of the opioid receptor antagonist naltrexone (0.1; 0.3; 1.0 mg/kg i.p.) on operant ethanol self-administration alone and in combination with the non-competitive NMDA antagonist memantine (0.5 and 1 mg/kg, i.p.) were studied in rats. Acute administration of naltrexone (0.1; 0.3; 1.0 mg/kg i.p.) inhibited ethanol self-administration in a dose-dependent manner. Memantine (1.0 mg/kg) significantly enhanced the effects of naltrexone at 0.1 mg/kg, failing per se to inhibit ethanol consumption. Thus, low, sub-effective dose of memantine in combination with low doses of naltrexone blocked the reinforcing properties of ethanol in rats. It is suggested that the combination of sub-effective doses of memantine and naltrexone may have therapeutic value in the treatment of alcoholism particularly in a subgroup of alcoholic patients who have high sensitivity to the adverse side effects of naltrexone.
Kuzmin
Alexander
A
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. alexander.kuzmin@neuro.ki.se
Stenback
Tove
T
Liljequist
Sture
S
D000428:Alcohol Drinking / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D000431:Ethanol / Q000008:administration & dosage*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008297:Male; D008559:Memantine / Q000008:administration & dosage / Q000494:pharmacology*; D023421:Models, Animal; D009271:Naltrexone / Q000008:administration & dosage / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D012054:Reinforcement, Psychology; D012646:Self Administration
D018691:Excitatory Amino Acid Antagonists; D009292:Narcotic Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; D009271:Naltrexone; D008559:Memantine