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Stimulation of central 5-HT1D receptors causes hypothermia in the guinea-pigDepartment of Neuropharmacology, Glaxo Group Research, Ware, Hertfordsire SG12 ODP
Glaxo Unit of Behavioural Psychopharmacology, Department of Biosciences, University of Hertfordshire, College Lane, Hatfield, Hertfordshire AL10 9AB
Glaxo Institute of Applied Pharmacology, Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QJ, UK The 5-HT1 receptor agonist GR46611 (3-30 mg/kg s.c.) caused a dose-related decrease in rectal temperature in the adult guinea-pig. A lower dose (20 µg) administered directly into the lateral cerebral ventricle also caused a hypothermic response, suggesting that this effect is centrally mediated. GR46611-induced (10 mg/kg s.c.) hypothermia was not attenuated by WAY100135 (3-10 mg/kg s.c.), ritanserin (0.3-1 mg/kg s.c.), spiperone (0.1-0.3 mg/kg s.c.) and ondansetron (0.1-1 mg/kg s.c.), suggesting that 5-HT1A, 5-HT2A, 5-HT 2C and 5-HT3 receptors are unlikely to be involved in this response. In contrast, the poorly selective 5-HT receptor antagonist, metergoline (1-10 mg/kg s.c.), and the potent 5-HT1D receptor antagonist, GR127935 (0.1-1 mg/kg p.o.), antagonized the effects of GR46611. The present data suggest that antagonism of GR46611-induced hypothermia may be useful for assessing the potency and duration of action of centrally-acting 5-HT 1D receptor antagonists in the guinea-pig.
Key Words: thermoregulation • guinea-pig • 5-HT • GR46611 • GR127935
Journal of Psychopharmacology, Vol. 8, No. 1,
14-21 (1994) |
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