GABA(A)-BENZODIAZEPINE RECEPTORS IN THE STRIATUM ARE INVOLVED IN THE SEDATION PRODUCED BY A MODERATE, BUT NOT AN INTOXICATING ETHANOL DOSE IN OUT-BRED WISTAR RATS

The role of the dorsal striatum in mediating the sedation produced by a moderate (0.75 g/kg) and an intoxicating (1.25 g/kg) EtOH dose was i nvestigated in the open field by determining the capacity of direct in trastriatal injections of RY 008, a partial inverse agonist of the ben zodiazepine (BDZ) receptor, to antagonize EtOH's effects. SR 95531, th e competitive high-affinity GABA(A) antagonist was used as a reference compound. Intrastriatal RY 008 (50, 500 ng) and SR 95531 (50 ng) anta gonized the sedation produced by the 0.75 g/kg EtOH dose. However, RY 008 did not alter the sedation produced by the 1.25 g/kg dose. RY 008 alone was without effect. RY 008 also failed to negatively modulate GA BAergic function at alpha 1 beta 2 gamma 2 or alpha 6 beta 2 gamma 2 r eceptor subtypes expressed in Xenopus oocytes. Intrastriatal modulatio n of the moderate EtOH dose was site specific: no antagonism by RY 008 after intraaccumbens infusions was observed. The results suggest that central GABA(A)-BDZ receptors in the dorsal striatum play an importan t role in mediating the sedation produced by a moderate EtOH dose in t he open field. (C) 1998 Elsevier Science B.V. All rights reserved.