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NEUROPHARMACOLOGY

Roles of 5-Hydroxytryptamine (5-HT) Receptor Subtypes in the Inhibitory Effects of 5-HT on C-Fiber Responses of Spinal Wide Dynamic Range Neurons in Rats

Neuroscience Research Institute and Department of Neurobiology, Peking University, Key Laboratory for Neuroscience, Ministry of Education, Beijing, People's Republic of China

5-Hydroxytryptamine (5-HT; serotonin) plays an important role in the descending control of nociception. 5-HT and its receptors have been extensively studied in the modulation of nociceptive transmission at the spinal level using behavioral tests that may be affected by the effects of 5-HT on motor performance and skin temperature. Using electrophysiological methods, the present study aimed to systematically investigate the roles of 5-HT receptor subtypes on the inhibitory effects of 5-HT on responses of the spinal wide dynamic range (WDR) neurons to C-fiber inputs in rats. Under basal conditions, topical application of 5-HT to the spinal cord inhibited the C-fiber responses of WDR neurons dose-dependently, whereas antagonists of 5-HT_1A [WAY 100635 [N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-cyclohexanecarboxamide maleate salt]], 5-HT_1B [GR 55562 [3-[3-(dimethylamino)propyl]-4-hydroxy-N-[4-(4-pyrid-dinyl)phenyl]benzamide dihydrochloride]], 5-HT_2A [ketanserin [3-[2-[4-(fluorobenzoyl)-1-piperidinyl]ethyl]-2,4[1H,3H]-quinazolinedione tartrate]], 5-HT_2C [RS 102221 [8-[5-(2,4-dimethoxy-5-(4-trifluoromethylphenylsulfonamido)phenyl-5-oxopentyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione hydrochloride]], 5-HT₃ [MDL 72222 [3-tropanyl-3,5-dichlorobenzoate]], and 5-HT₄ [GR 113808 ([1-[2-[(methylsulfonyl)-amino]ethyl]-4-piperidinyl]methyl 1-methyl-1H-indole-3-carboxylate)] had no effect on their own. The inhibitory effects of 5-HT were reversed by antagonists of 5-HT_1B (GR 55562), 5-HT_2A (ketanserin), 5-HT_2C (RS 102221), 5-HT₃ (MDL 72222), and 5-HT₄ (GR 113808) but not by 5-HT_1A (WAY 100635) receptor antagonists. Topical administration of agonists of 5-HT_1A [(2R)-(+)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide], 5-HT_1B [CGS 12066 [7-trifluoromethyl-4-(4-methyl-1-piperazinyl)pyrrolo-[1,2-a]quinoxaline maleate salt]], 5-HT_2A (-methyl-5-hydroxytryptamine maleate), 5-HT_2C [MK 212 [6-chloro-2-(1-piperazinyl)pyrazine hydrochloride]], 5-HT₃ [1-(3-chlorophenyl)biguanide hydrochloride], and 5-HT₄ [2-[1-(4-piperonyl)piperazinyl]benzothiazole] also inhibited the C-responses. These results suggest that, under basal conditions, there is no tonic serotonergic inhibition on the C-responses of dorsal horn neurons, and multiple 5-HT receptor subtypes including 1B, 2A, 2C, 3, and 4 may be involved in mediating the inhibitory effects of 5-HT.

Address correspondence to: Dr. You Wan, Neuroscience Research Institute, Peking University, 38 Xue-Yuan Road, Beijing 100083, People's Republic of China. E-mail: ywan{at}bjmu.edu.cn