TY - JOUR T1 - Evidence for Involvement of Central 5-HT<sub>4</sub> Receptors in Cholinergic Function Associated with Cognitive Processes: Behavioral, Electrophysiological, and Neurochemical Studies JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 676 LP - 682 VL - 296 IS - 3 AU - Machiko Matsumoto AU - Hiroko Togashi AU - Kiyoshi Mori AU - Ken-ichi Ueno AU - Satoshi Ohashi AU - Taku Kojima AU - Mitsuhiro Yoshioka Y1 - 2001/03/01 UR - http://jpet.aspetjournals.org/content/296/3/676.abstract N2 - The possible involvement of 5-HT4 receptors in cognitive function was investigated with a view toward modulating the cholinergic neuronal system. For this purpose, behavioral, electrophysiological, and neurochemical studies were performed in rats. The behavioral study, using a passive avoidance test, demonstrated that the 5-HT4receptor agonist SC 53116 (10 μg/rat i.c.v.) had an ameliorative effect on the muscarinic receptor antagonist scopolamine-induced (1 mg/kg i.p.) impairment of learning. The electrophysiological study showed that SC 53116 (1 and 10 μg/rat i.c.v.) enhanced the population spike amplitude in the hippocampal CA1 field evoked by Schaffer collateral stimulation. SC 53116 (10 μg/rat i.c.v.) also augmented the tetanus-induced long-term potentiation (LTP). This augmented LTP was blocked not only by the selective 5-HT4 receptor antagonist GR 113808 (20 μg/rat i.c.v.) but also by scopolamine (1 mg/kg i.p.). These findings suggest that the functional interaction between the serotonergic system mediated via 5-HT4receptors and the cholinergic system associated with cognitive processes exists in vivo. This possibility was further strengthened by neurochemical study using in vivo microdialysis; local administration of SC 53116 (10 and 100 μM) concentration-dependently enhanced the extracellular levels of acetylcholine (ACh) in the hippocampus. SC 53116-induced (10 μM) facilitation of ACh release was prevented by coperfusion of GR 113808 (10 μM). Taken together, the present findings obtained by these different approaches indicate the possibility that the 5-HT4 receptors are involved in cognitive impairment induced by the cholinergic neuronal system. The American Society for Pharmacology and Experimental Therapeutics ER -