Involvement of 5-HT1A and 5-HT1B receptors for citalopram-induced hypothermia in the rat

OBJECTIVES: To examine the role of 5-HT1A and 5-HT1B receptors for citalopram-induced hypothermia in the rat. METHODS: Core temperature measurements were performed in adult male Wistar rats (305-340 g) using a computer-assisted recording instrument. The temperature readings were automated and gave a printout when the core temperature had stabilised at +/- 0.1 degree C for 10 s. RESULTS: Citalopram (6.25-100.0 mumol/kg) produced a dose-dependent hypothermia. The effect was maximal within 60 min after administration, and had waned off at 120 min. The 5-HT1B receptor agonist anpirtoline (0.25-4.0 mumol/kg) produced a dose-dependent decrease in core temperature. The citalopram-induced hypothermia (25 mumol/kg) was antagonised by pretreatment with either of the 5-HT1A and the 5-HT1B receptor antagonists, WAY-100,635 (0.04 mumol/kg) and NAS-181 (1.0 mumol/kg), respectively, or by the two drugs in combination. Subchronic treatment with the SSRI zimeldine (100 mumol/kg once daily for 2 weeks) resulted in tolerance to the hypothermic effect of citalopram (100 mumol/kg). CONCLUSIONS: The hypothermia produced by acute administration of the SSRI citalopram is mediated via activation of 5-HT1A, as well as 5-HT1B receptors, and this effect is subject to the development of tolerance.