Assessment of Effects of α2-Adrenoceptor Agonists and Antagonists in Dorsal Hippocampus on Muscimol State-dependent Memory

Abstract

Background and Objectives: Adrenergic and GABAergic systems of the brain play an important role in memory and learning. According to results of studies, morphine, histamine, and lithium induce state-dependent learning. This study was conducted aiming at assessing the effects of α2-adrenergic receptors of CA1 on muscimol state-dependent learning. Methods: In this study, clonidine as agonist and yohimbine as antagonist of α2-adrenergic receptor, muscimol as agonist of GABA A receptor and step-through inhibitory avoidance task as a model of learning were used for memory assessment. The data analyzed using one-way analysis of variance, t-test, and Mann-Whitney test. In all statistical assessments, p<0.05 was considered as significance level in the comparison of the groups. Results: Pre-test intra-CA1 injection of muscimol (1.2µg/mice) impaired inhibitory avoidance memory on the test day (p<0.01). Pre-test injection of muscimol (0.06 and 1.2µg/mice) reversed the memory impaired under pre-training muscimol (1.2µg/mice); so, muscimol can induce state-dependent learning (p<0.001). Pre-training injection of clonidine (0.6 and 1.2μg/mice) also reversed pre-training muscimol (1.2µg/mice, intra-CA1) induced amnesia (p<0.01). Also pre-test intra-CA1 injection of yohimbine (1.2 and 2.4μg/mice) 2 minutes before administration of effective dose of muscimol inhibited muscimol state-dependent memory (p<0.01). Conclusion: Overall, It can be concluded that α2-adrenergic receptors of dorsal hippocampus have an important role in muscimol state-dependent learning on the test day.

Keywords

• muscimol
• alpha-2-adrenoceptor
• hippocampus
• learning
• state-dependen learningt