Role of CA1 GABA and GABA receptors on learning deficit induced by D-AP5 in passive avoidance step-through task.

To investigate the interaction between hippocampal γ-aminobutyric acid GABA receptor (GABAR) or GABA receptor (GABAR) and N-methyl-D-aspartate receptor (NMDAR) in the acquisition of passive avoidance memory in rats, we used GABA or GABA agents, D-AP5 (as a NMDAR antagonist), and a combination of the mentioned drugs in a step-through task. All agents were microinjected into the intra-CA1 regions at a volume of 1 µl/rat, prior to training. GABAR agonist muscimol (0.2 µg/rat), selective GABAR agonist baclofen (0.5 µg/rat) or NMDAR antagonist D-AP5 (0.25 µg/rat) decreased step-through latency, indicating a memory retention impairment. Neither GABAR antagonist bicuculline (0.0625-0.25 µg/rat) nor GABAR antagonist phaclofen (0.1-0.5 µg/rat) altered memory retrieval by itself. Moreover, the lower dose of muscimol (0.05 µg/rat) decreased D-AP5 (0.125 µg/rat) response on memory acquisition, but bicuculline did not alter the D-AP5 response. Furthermore, baclofen and phaclofen at the dose of 0.1 µg/rat potentiated D-AP5 response at the doses of 0.0625 and 0.125 µg/rat, but abolished memory impairment induced by D-AP5 at the higher dose (0.25 µg/rat). The results suggest that the microinjection of GABA and GABA agents into the CA1 region differently affects memory acquisition deficit induced by D-AP5. The activation of GABARs increased the impairment effect of D-AP5 on passive avoidance memory, but their blockade did not have an effect. Also, the activation or blockade of GABARs induced a similar and dual effect.