Stimulation of GABAB 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 contribution 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 components. 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 working-memory component for Expt. 1 required travelling to the goal arm diagonally 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 preceding trial, with 0- and 15-s delays between trials. In Expt. 1, pretrained rats (n = 8) received the GABAA agonist, muscimol (0.1 microgram in 0.5 microliter), the GABAB agonist, R(+)-baclofen (0.01, 0.05 and 0.1 microgram), and its less active enantiomer, S(-)-baclofen (0.1 microgram), in a counterbalanced order with retraining to criterion between injections. In Expt. 2, pretrained rats (n = 9) received saline (0.5 microliter), R(+)-baclofen (0.1 microgram), the GABAB antagonist, phaclofen (1 microgram), and R(+)-baclofen+phaclofen. Results of Expt. 1 revealed that intra-nbm muscimol and, in a dose-dependent manner, R(+)-baclofen differentially affected working but not reference memory. In Expt. 2, the differential mnemonic impairment produced by R(+)-baclofen was replicated and co-injection with phaclofen reversed this effect. A 15-s delay between trials significantly impaired working but not reference memory. Results suggest that both GABAA and GABAB receptors may be involved in modulating the possible mnemonic functions of nbm cholinergic neurons.