STIMULATION OF GABA(B) RECEPTORS IN THE BASAL FOREBRAIN SELECTIVELY IMPAIRS WORKING-MEMORY OF RATS IN THE DOUBLE Y-MAZE

The present experiments were conducted to evaluate the possible contri bution of GABAergic inputs to the basal forebrain in the region of the nucleus basalis magnocellularis (nbm) to memory. In two experiments, rats implanted with bilateral intra-nbm guide cannulae were trained in the double Y-maze task to perform working- and reference-memory compo nents. Animals were placed in one of two start arms of the first ''Y'' and the reference-memory component required travelling to its central stem for food. Access to the second ''Y'' then was given and the work ing-memory component for Expt. 1 required travelling to the goal arm d iagonally opposite the start arm in the first ''Y'' of that trial. In Expt. 2, the working-memory component required travelling to the goal arm opposite to the goal arm entered in the second ''Y'' on the preced ing trial, with 0- and 15-s delays between trials. In Expt. 1, pretrai ned rats (n = 8) received the GABA(A) agonist, muscimol (0.1 mug in 0. 5 mul), the GABA(B) agonist, R(+)-baclofen (0.01, 0.05 and 0.1 mug), a nd its less active enantiomer, S(-)-baclofen (0.1 ug), in a counterbal anced order with retraining to criterion between injections. In Expt. 2, pretrained rats (n = 9) received saline (0.5 mul), R(+)-baclofen (0 .1 mug), the GABA(B) antagonist, phaclofen (1 mug), and R(+)-baclofen + phaclofen. Results of Expt. 1 revealed that intra-nbm muscimol and, in a dose-dependent manner, R(+)-baclofen differentially affected work ing but not reference memory. In Expt. 2, the differential mnemonic im pairment produced by R(+)-baclofen was replicated and co-injection wit h phaclofen reversed this effect. A 15-s delay between trials signific antly impaired working but not reference memory. Results suggest that both GABA(A) and GABA(B) receptors may be involved in modulating the p ossible mnemonic functions of nbm cholinergic neurons.