Effects of the 5-HT1 receptor agonists DP-5-CT, CGS 12066B, and RU 24969 on plasma adrenaline and glucose levels in the rat

Abstract

Recent results have indicated that the 5-HT1A receptor subtype mediates the adrenaline-releasing and hyperglycemic effects of 8-hydroxy-2-(di-n-propylamino)tetralin in the rat. The aim of this study was to analyse, by means of the peripherally acting 5-HT1A receptor agonist, N,N-dipropyl-5-carboxamidotryptamine (DP-5-CT), whether these 5-HT1A receptors are peripherally or centrally localised. In view of the appreciable affinity of DP-5-CT for the 5-HT1D receptor subtype, the effects of the mixed 5-HT1B/5-HT1D receptor agonist 7-trifluoromethyl-4-(4-methyl-1-piperazinyl)-pyrrolo(1,2-a)quinoxaline (CGS 12066B), and the mixed 5-HT1A/5-HT1B/5-HT1D receptor agonist 5-methoxy-3(1,2,3,6-tetrahydropyridine-4-yl)1H-indole (RU 24969) were also investigated. Administration of DP-5-CT (0.3 and 1 mg/kg i.v.) increased plasma glucose levels dose-dependently, whereas only the 1 mg/kg dose of DP-5-CT elicited a rise in plasma adrenaline levels. In contrast, CGS 12066B (1.5 and 4.5 mg/kg i.v.) did not affect either plasma adrenaline or plasma glucose levels. Administration of RU 24969 (0.5-4.5 mg/kg i.v.) increased dose-dependently both plasma adrenaline and glucose levels. The data suggest that central 5-HT1A receptors, but neither 5-HT1B nor 5-HT1D receptors, regulate plasma adrenaline and glucose levels.