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

Growing evidence indicates that antagonists of the 5-hydroxytryptamine (serotonin) receptor₆ (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.