5-HT(6) receptor agonists and antagonists enhance learning and memory in a conditioned emotion response paradigm by modulation of cholinergic and glutamatergic mechanisms.

British Journal of Pharmacology
S WoodsKevin C F Fone

Abstract

5-HT(6) receptors are abundant in the hippocampus, nucleus accumbens and striatum, supporting their role in learning and memory. Selective 5-HT(6) receptor antagonists produce pro-cognitive effects in several learning and memory paradigms while 5-HT(6) receptor agonists have been found to enhance and impair memory. The conditioned emotion response (CER) paradigm was validated in rats. Then we examined the effect of the 5-HT(6) receptor antagonist, EMD 386088 (10 mg·kg(-1) , i.p.), and agonists, E-6801 (2.5 mg·kg(-1) , i.p.) and EMD 386088 (5 mg·kg(-1) , i.p.) on CER-induced behaviour either alone or after induction of memory impairment by the muscarinic receptor antagonist, scopolamine (0.3 mg·kg(-1) , i.p) or the NMDA receptor antagonist, MK-801 (0.1 mg·kg(-1) , i.p). Pairing unavoidable foot shocks with a light and tone cue during CER training induced a robust freezing response, providing a quantitative index of contextual memory when the rat was returned to the shock chamber 24 h later. Pretreatment (-20 min pre-training) with scopolamine or MK-801 reduced contextual freezing 24 h after CER training, showing production of memory impairment. Immediate post-training administration of 5-HT(6) receptor antagonist, SB-270146, and...Continue Reading

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