Modulation of muscimol state-dependent memory by α2-adrenoceptors of the dorsal hippocampal area

Abstract

In the present study, the effects of bilateral intra-dorsal hippocampal (intra-CA1) injections of α2-adrenoceptor agonist and antagonist, on muscimol state-dependent memory were examined in mice. A single-trial step-down passive avoidance task was used for the assessment of memory retention in adult male NMRI mice. Administration of muscimol (0.1μg/mouse, intra-CA1) 15min before training or testing induced impairment of memory retention. Injection of the same dose of the drug 15min before testing restored memory retention impaired under pre-training muscimol influence. Pre-test intra-CA1 administration of the α2-adrenoceptor agonist clonidine (0.5 and 1μg/mouse) impaired memory retention, although the low dose of the drug (0.25μg/mouse) did not affect memory retention. Pre-test intra-CA1 administration of the α2-adrenoceptor antagonist yohimbine (1 and 2μg/mouse) improved memory retention, although the low dose of the drug (0.5μg/mouse) did not affect memory retention. In other series of experiments, pre-test co-administration of certain doses of clonidine (0.125 and 0.25μg/mouse, intra-CA1), doses which were ineffective when given alone, and muscimol (0.1μg/mouse, intra-CA1) significantly inhibited muscimol state-dependent memory. Pre-test intra-CA1 administration of certain doses of yohimbine (0.25 and 0.5μg/mouse), doses which were ineffective when given alone, improved pre-training muscimol (0.1μg/mouse)-induced retrieval impairment. Moreover, pre-test co-administration of yohimbine (0.25 and 0.5μg/mouse, intra-CA1) and muscimol (0.025μg/mouse, intra-CA1), an ineffective dose, significantly restored the retrieval and induced muscimol state-dependent memory. It may be concluded that the α2-adrenoceptors of the dorsal hippocampal area play an important role in muscimol state-dependent memory.