Time-course of 5-HT6 receptor mRNA expression during memory consolidation and amnesia

Growing evidence indicates that antagonists of the 5-hydroxytryptamine (serotonin) receptort(6) (5-HT6) improve memory and reverse amnesia although the mechanisms involved are poorly understood. Hence, in this paper RT-PCR was used to evaluate changes in mRNA expression of 5-HT6 receptor in trained and untrained rats treated with the 5-HT6 receptor antagonist SB-399885 and amnesic drugs scopolamine or dizocilpine. Changes in mRNA expression of 5-HT6 receptor were investigated at different times in prefrontal cortex, hippocampus and striatum. Data indicated that memory in the Pavlovian/instrumental autoshaping task was a progressive process associated to reduced mRNA expression of 5-HT6 receptor in the three structures examined. SB-399885 improved long-term memory at 48 h, while the muscarinic receptor antagonist scopolamine or the non-competitive NMDA receptor antagonist dizocilpine impaired it at 24 h. Autoshaping training and treatment with SB-399885 increased 5-HT6 receptor mRNA expression in (maximum increase) prefrontal cortex and striatum, 24 or 48 h. The scopolamine-induced amnesia suppressed 5-HT6 receptor mRNA expression while the dizocilpine-induced amnesia did not modify 5-HT6 receptor mRNA expression. SB-399885 and scopolamine or dizocilpine were able to reestablish memory and 5-HT6 receptor mRNA expression. These data confirmed previous memory evidence and of more interest is the observation that training, SB-399885 and amnesic drugs modulated 5-HT6 receptor mRNA expression in prefrontal cortex, hippocampus and striatum. Further investigation in different memory tasks, times and amnesia models together with more complex control groups might provide further clues. (C) 2009 Elsevier Inc. All rights reserved.