Involvement of 5-HT1A and 5-HT1B receptors for citalopram-induced hypothermia in the rat.
OBJECTIVE
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.
Oerther
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Department of Physiology and Pharmacology, Division of Pharmacology, Karolinska Institutet, 17177 Stockholm, Sweden.
Ahlenius
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D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects* / Q000502:physiology; D015283:Citalopram / Q000494:pharmacology*; D007035:Hypothermia / Q000139:chemically induced*; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D001578:Benzopyrans; D015283:Citalopram; D009025:Morpholines; D010879:Piperazines; D011725:Pyridines; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; C112429:2-(((3-(morpholinylmethyl)-2H-chromen-8-yl)oxy)methyl)morpholine; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide