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 possibil ity that the reinforcing effects of ethanol may be, at least partially , mediated via these receptor ionophores. In this study, a multiple sc hedule 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 conducte d with ethanol, NMDA antagonists and GABA agonists given before six co nsecutive sessions. Pretreatment with ethanol selectively decreased et hanol self-administration without altering saccharin self-administrati on, The competitive NMDA antagonist CPPene (2-carboxypiperazine-4-yl)- 1-propenyl-1-phosphonic acid [SDZ EAA 494]) and the noncompetitive NMD A antagonist phencyclidine decreased both ethanol and saccharin self-a dministration. The GABA agonists pentobarbital and diazepam also faile d to reduce ethanol self-administration, relative to saccharin. Althou gh these results do not support the hypothesis that antagonism of the NMDA receptor system or activation of the GABA receptor system can sel ectively modify ethanol-reinforced responding, they identify important issues for designing the best strategies to be used to assess selecti ve drug effects on ethanol self-administration.