The pharmacology of the hypothermic response in mice to 8-hydroxy-2-(DI-n-propylamino)tetralin (8-OH-DPAT) : A model of presynaptic 5-HT1 function

In the mouse, injection (subcutaneously) of the putative 5-HT₁ agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), produced a dose-related hypothermia (ED₅₀:0.36mg/kg). A maximum response was elicited by intracerebroventricular (i.c.v.) injection of 8-OH-DPAT (3 μg) and almost abolished by lesion of 5-HT-containing terminals in the brain with 5,7-dihydroxytryptamine (5,7-DHT; i.c.v.) or long-term treatment with p-chlorophenylalanine. The response was unaltered by a range of neurotransmitter antagonists: prazosin (α₁-adrenoceptor), idazoxan (α₂-adrenoceptor), metoprolol (β₁-adrenoceptor), erythro-dl-1-(7-methylindan-4-yloxy)-3-isopropylamino-butan-2-ol (β₂-adrenoceptor), (?)propranolol or (±)pindolol (β-adrenoceptor), flupenthixol (dopamine) or Ro 15–1788 (benzodiazepine binding site). Classical 5-HT antagonists (methysergide, metergoline, cinanserin and methiothepin) were either without effect or facilitated the response and the 5-HT₂ antagonist, ritanserin was also without effect. In contrast, quipazine and haloperidol produced a dose-related antagonism of the response.Since the response was almost abolished by a lesion induced by 5,7-DHT and was antagonised by quipazine, which is known to antagonise presynaptic 5-HT function in vitro, it is suggested that the hypothermie response is due to 8-OH-DPAT acting as an agonist at a presynaptic 5-HT receptor, which also appears to be sensitive to butyrophenones (the antagonism elicited by haloperidol but not by flupenthixol). The hypothermie response of mice to 8-OH-DPAT, therefore, may provide a simple and convenient in vivo model in which to measure the function of the presynaptic 5-HT receptor.