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MATERIALS AND METHODS - HAL - INSERM Accueil：材料和方法-哈尔INSERM的欢迎.doc

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PAGE PAGE 29 Tachykinin regulation of cholinergic transmission in the limbic/prefrontal territory of the rat dorsal striatum: implication of new neurokinine 1-sensitive receptor binding site and interaction with enkephalin/mu opioid receptor transmission Sylvie Pérez, Adrienne Tierney, Jean-Michel Deniau, and Marie-Louise Kemel INSERM, U667, Collège de France, Paris, F-75231 France?; Univ Pierre et Marie Curie, Paris, F-75005, France. Tel: (33) 01 44 27 12 16 Fax: (33) 01 44 27 12 60 Corresponding author: Marie-Louise Kemel INSERM U667, Collège de France, 11 place Marcelin Berthelot 75231 Paris, France; e-mail: marie-lou.kemel@college-de-france.fr Abbreviation: ?-methyl-p-tyrosine, ?MPT; ?funaltrexamine, ?FNA?; acetylcholine, ACh?; choline acetyl transferase, ChAT?; dopamine, DA?; enkephalin, ENK?; mu opioid receptor, MOR?; neurokinin, NK; NK1 receptor, NK1R?; prefrontal, PF?; substance P, SP, ABSTRACT The tachykinin neurokinin 1 receptors (NK1Rs) regulation of acetylcholine release and its interaction with the enkephalin/mu opioid receptors (MORs) transmission was investigated in the limbic/prefrontal territory of the dorsal striatum. Using double immunohistochemistry, we first showed that in this territory, cholinergic interneurons contain tachykinin NK1Rs and co-express MORs in the last part of the light period (afternoon). In slices of the striatal limbic/prefrontal territory, following suppression of the dopaminergic inhibitory control of acetylcholine release, application of the tachykinin NK1R antagonist, SSR240600, markedly reduced the NMDA-induced acetylcholine release in the morning but not in the afternoon when the enkephalin/MOR regulation is operational. In the afternoon, the NK1R antagonist response required the suppression of the enkephalin/MOR inhibitory control of acetylcholine release by ?funaltrexamine. The pharmacological profile of the tachykinin NK1R regulation tested by application of the receptor agonists ([Pro9]substance P, ne