Involvement of Raphe-Hippocampal Serotonergic and Septo-Hippocampal Cholinergic Mechanisms in the Penile Erection Induced by FR 121196, a Putative Cognitive Enhancer

The Japanese Journal of Pharmacology

Isamu Yamaguchi¹  Mayako Yamazaki¹  Nobuya Matsuoka¹  Noriaki Maeda¹ 

[1] Basic Research Group, Fujisawa Pharmaceutical Co., Ltd.

关键词: FR121196;    Penile erection;    Septo-hippocampal pathway;    Median- and dorsal-raphe nuclei;   

DOI  :  10.1254/jjp.68.85

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(41)Cited-By(2)FR121196 (N-[4-acetyl-1-piperazinyl]-4-fluorobenzenesulfonamide), a putative cognitive enhancer, induced penile erection in naive rats; the dose-response curve was bell-shaped with the maximum response obtained at the dose of 3.2 mg/kg. The response to FR121196 was abolished in rats treated with intra-raphe injections of 5, 7-dihydroxytryptamine or systemic injections of p-chlorphenylalanine (150 mg/kg, i.p. for three consecutive days) as well as in rats with electrolytic medial-septum lesion or surgical fimbria-fornix lesion. In addition, the penile erection induced by FR121196 (3.2 mg/kg) was dose-dependently attenuated by pindolol (0.1- 3.2 mg/kg), a serotonin (5-HT)1 antagonist with β-antagonistic activity, but not by metoprolol, a selective β-antagonist. The inhibitory activity was shared by ICS205-930, a 5-HT3 antagonist, but not by ketanserin, a 5-HT2 antagonist, or sulpiride, a dopamine D2 antagonist. Scopolamine (0.032-1 mg/kg), but not methyl-scopolamine (0.032-1 mg/kg), also attenuated the penile erection induced by FR121196. Neurochemical analysis revealed that intraperitoneal injection of FR121196 significantly elevated the levels of 5-HT and its major metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the hippocampus and that raphe-lesion significantly reduced both 5-HT and 5-HIAA levels without affecting choline-acetyltransferase activity in all cortical and subcortical regions examined. It is thus postulated that FR121196 facilitates the raphe-hippocampal serotonergic pathway resulting in an activation of the septo-hippocampal cholinergic pathway and finally induces the penile erectile response.

【 授权许可】

Unknown