Effects of intrahippocampal injection of GABAergic drugs on memory retention of passive avoidance learning in rats

The effect of post-training intrahippocampal injection of gamma-aminobutyric acid (GABA) receptor agonists and antagonists, immediately after a training session on memory retention of passive avoidance learning in rats, was measured in the presence and absence of physostigmine. Post-training treatments were carried out in all the experiments. The different doses of the GABA(A) receptor agonist muscimol (2, 4 and 6 mug/rat) decreased memory retention in rats dose-dependently. The higher response was obtained with 6 mug/rat of the drug. When the GABA(A) receptor antagonist bicuculline (0.5, 1, 2 and 4 mug/rat) was administered, only one dose of the drug (1 mug/rat) increased memory retention; however, the antagonist reduced the effect of muscimol. The GABA(B) receptor agonist, baclofen (0.25, 0.5, 1 and 2 mug/rat) also reduced memory retention in the animals. Intrahippocampal injection of lower doses of the GABAB receptor antagonist CGP35348 (P-[3-aminopropyl]-p-diethoxymethyl-phosphinic acid) (2.5, 5, 10 mug/rat) did not effect memory retention, although the higher doses of the drug (25 and 50 mug/rat) decreased memory retention. The doses of antagonist (2.5, 5 and 10 mug/rat), which did not elicit any response alone, reduced the effect of baclofen. The inhibitory response of CGP35348 was also decreased by bicuculline. In another series of experiments, physostigmine improved memory retention. The GABA receptor agonists, muscimol and baclofen, as well as the GABA receptor antagonists bicuculline and CGP35348, decreased the effect of physostigmine. Atropine decreased memory retention by itself and potentiated the response of muscimol and baclofen. It is concluded that GABAA and GABAB receptor activation may be involved in the impairment of memory retention.