Role of Hippocampal 5-HT6 Receptors in Glucocorticoid-Induced Enhancement of Memory Consolidation in Rats

Introduction: of the study: Post-training administration of glucocorticoids enhance memory consolidation of inhibitory avoidance learning. Given the involvement of 5-HT6 receptors in memory processing and the interaction of glucocorticoids with the brain serotonergic system in modulating memory processing, we investigated whether the effect of glucocorticoids on the consolidation of emotionally arousing training depends on hippocampal 5-HT6 receptors. Methods: Rats were trained in an inhibitory avoidance task and immediately received the systemic injections of corticosterone (CORT) as well as the intra-hippocampal injections of 5-HT receptors agonist or antagonist. The memory retention test was done 48 hours after training and immediately after the behavioral test, the animals were sacrificed and the hippocampi (left and right) rapidly dissected out for molecular studies. Results: Post-training injections of different doses of CORT (1.25, 2.5, 5, and 10 mg/kg) enhanced memory retention in a dose-dependent manner. The CORT-induced enhancement of memory consolidation was blocked by bilateral intra-hippocampal injections of 5-HT6 receptor antagonist SB271046 (5 or 10 ng/per side), but not agonist EMD386088 (5 or 10 ng/per side). Furthermore, systemic CORT reduced 5-HT6 receptor mRNA and protein expression in the hippocampus. Both doses of 5-HT6 receptor agonist and antagonist significantly enhanced and reduced the expression of the 5-HT6 receptor, respectively, and both ligands at the higher dose (10 ng) enhanced memory consolidation. Moreover, CORT injection attenuated and enhanced, respectively, the effects of agonist and antagonist on 5-HT6 receptor expression. Conclusion: These behavioral and molecular findings indicated an interaction between glucocorticoids and hippocampal 5-HT6 receptors in the consolidation of emotionally arousing experiences.