The effects of the 5-HT(6) receptor agonist EMD and the 5-HT(7) receptor agonist AS19 on memory formation

Growing evidence indicates that 5-hydrohytryptamine (5-HT) receptors mediate learning and memory. Particularly interesting are 5-HT(6) and 5-HT(7) receptors, which are localized in brain areas involved in memory formation. Interestingly, recently selective 5-HT(6) and 5-HT(7) receptor agonists and antagonists have become available. Previous evidence indicates that 5-HT(6) or 5-HT(7) receptors antagonists had no effects, improved memory formation and/or reversed amnesia. Herein, the effects of EMD (a 5-HT(6) receptor agonist) and AS19 (a 5-HT(7) receptor agonist) in the associative learning task of autoshaping were studied. Post-training systemic administration of EMD (1-10 mg/kg) or AS19 (1-10 mg/kg) were tested in short-term memory (STM) and long-term memory (LTM). Results showed that only EMD 5.0mg/kg impaired both STM and LTM. AS19 at 1-10 mg/kg significantly impaired STM but not LTM. In those groups used to test only LTM, EMD impaired it; while AS19 improved LTM. Moreover, in the interaction experiments, the STM EMD-impairment effect was partially reversed by the selective 5-HT(6) receptor antagonist SB-399885 (10 mg/kg). The STM AS19-impairment effect (5.0 mg/kg) was not altered by the selective 5-HT(1A) antagonist WAY 100635 (0.3 mg/kg) but reversed by the selective 5-HT(7) receptor antagonist SB-269970 (10.0 mg/kg). The AS19-SB-269970 combination impaired LTM. Taken together these data suggest that the stimulation of 5-HT(6) impaired both STM and LTM. 5-HT(7) receptors stimulation impaired STM but improved LTM. And these results are discussed in the context of their possible neural bases.