Effects of gamma-aminobutyric acid agonists and N-methyl-D-aspartate antagonists on a multiple schedule of ethanol and saccharin self-administration in rats.
Recently, it has been shown at both the cellular and behavioral levels that ethanol has effects on the N-methyl-D-aspartate (NMDA) and gamma-aminobutyric acid (GABA)a receptor systems, leading to the possibility that the reinforcing effects of ethanol may be, at least partially, mediated via these receptor ionophores. In this study, a multiple schedule of ethanol and saccharin self-administration was used to study that possibility. Adult male Long-Evans rats were trained during 1-hr sessions to press on two different levers for 10% (w/v) ethanol and 0.1% (w/v) saccharin solutions, under an alternating 5-min, fixed-ratio-4 schedule of liquid availability. After training, tests were conducted with ethanol, NMDA antagonists and GABA agonists given before six consecutive sessions. Pretreatment with ethanol selectively decreased ethanol self-administration without altering saccharin self-administration. The competitive NMDA antagonist CPPene (D-3-(2-carboxypiperazine-4-yl)-1-propenyl-1-phosphonic acid [SDZ EAA 494]) and the noncompetitive NMDA antagonist phencyclidine decreased both ethanol and saccharin self-administration. The GABA agonists pentobarbital and diazepam also failed to reduce ethanol self-administration, relative to saccharin. Although these results do not support the hypothesis that antagonism of the NMDA receptor system or activation of the GABA receptor system can selectively modify ethanol-reinforced responding, they identify important issues for designing the best strategies to be used to assess selective drug effects on ethanol self-administration.
Shelton
K L
KL
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0310, USA.
Balster
R L
RL
D000818:Animals; D003975:Diazepam / Q000494:pharmacology; D004327:Drinking Behavior; D000431:Ethanol / Q000008:administration & dosage*; D018755:GABA Agonists / Q000494:pharmacology*; D008297:Male; D010424:Pentobarbital / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012439:Saccharin / Q000008:administration & dosage*; D012646:Self Administration; D014867:Water
D018755:GABA Agonists; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D014867:Water; C065286:SDZ EAA 494; D000431:Ethanol; D012439:Saccharin; D010424:Pentobarbital; D010622:Phencyclidine; D003975:Diazepam