An interaction between serotonergic receptors (5HT6) with acute stress and corticosterone on retrieval and extinction of fear memory in mice

Recent studies indicated that serotonergic receptor can modulate of acute stres's and corticosterone effects on behavior processes especially learning and memory. The aim of this study determines the role of serotonergic receptors (5HT6) on effects of acute stress and corticosterone on fear-based memory retrieval and extinction in passive avoidance task. Male adult mice were trained and tested in an inhibitory avoidance task (footshock, 1mA 3s). For retrieval assessment, 30 min before corticosterone injection or application acute stress and one hour before retention test (48 hr after training) the animals received SC203575 as a 5HT6 receptor agonist or SB271046 as an antagonist of 5HT6 receptors. For assessment memory extinction, one hour before memory reactivation (48 hr after training) animal received the above drugs and then received corticosterone or acute stress. Memory retention test was done 2, 5, 7 and 9 days after memory reactivation. The results show that injection of corticosterone or application of acute stress before memory riactivation impaired memory retrieval and facilitated extinction of memory in subsequent tests. Pre-treatment with serotonergic receptors (5HT6) agonist and antagonist inhibited the effects of corticosterone or acute stress on memory retrieval and extinction, respectively. These findings indicate that the effects of glucocorticoids or acute stress on memory retrieval and extinction modulated at least, in part, by 5HT6 receptors.