ALCOHOL AND GABA - ETHANOL INTAKE MODIFIES HIPPOCAMPAL NIPECOTIC ACID BINDING IN ETHANOL-PREFERRING AND NONPREFERRING RATS

Summary— 3H‐nipecotic acid (3H‐NIP) binding to GABA uptake recognition sites was studied in the hippocampus of 3 groups of male, Long Evans rats: Group 1: ethanol‐naive rats (ENR); Group II: ethanol‐preferring rats (DR) and non‐preferring rats (NDR), which had consumed about 5 g.kg−1.d−1 and 1 g−1.d−1 of alcohol respectively in the form of a 12% ethanol solution prior to 3H‐NIP binding analysis; Group III: DR and NDR who had had no access to ethanol for 21 d after the initial exposure of ethanol solution (28 d). Binding studies showed that ethanol drunk by both DR and NDR in Group II decreased 3H‐NIP binding (Bmax decreased) with an enhancement of affinity (KD decreased). In rats subjected to withdrawal of ethanol (Group III), affinity of 3H‐NIP for GABA uptake sites was higher than in controls (Group I), but lower than in Group II, Bmax in this group being higher than in the 2 other groups. In Group III, KD was higher in DR than in NDR. These results showed that ethanol intake, in a free‐choice paradigm, altered 3H‐NIP binding, and that differences in ethanol intake between DR and NDR were associated with differences in sensitivity of hippocampal GABA uptake sites. These differences in 3H‐NIP binding could either precede ethanol intake, or be a direct result from it. The results, together with data from other laboratories suggest that: 1), 3H‐NIP binding sites are involved in the regulation of ethanol intake; 2), 1 factor responsible for individual differences in ethanol response is reflected by the GABA uptake system. 1990 Société Française de Pharmacologie et de Thérapeutique