Evidence that 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced hyperthermia in rats is mediated by stimulation of 5-HT2A receptors

The effects of various 5-HT receptor subtype-selective antagonists were studied on phenylisopropylamine hallucinogen1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced hyperthermia in Wistar rats, in an attempt to characterize the 5-HT receptor subtype mediating DOI-induced hyperthermia. Intraperitoneal administration of DOI to rats produced hyperthermia with a peak effect at 60 min. Pretreatment with propranolol (-adrenoceptor antagonist that also has binding affinity for 5-HT_1A, 5-HT_1B and 5-HT_2C sites), MDL-72222 or ondansetron (5-HT₃ antagonists) did not attenuate DOI-induced hyperthermia. In contrast, pretreatment with metergoline (5-HT₁/5-HT₂ antagonist), ketanserin, LY53857, mesulergine, mianserin and ritanserin (5-HT_2C/5-HT_2A antagonists), as well as spiperone (5-HT_1A/5-HT_2A/D₂ antagonist), significantly attenuated DOI-induced hyperthermia. Furthermore, daily administration of DOI (2.5 mg/kg per day) for 17 days did not produce either tolerance to its hyperthermic effect or modifym-CPP-induced hyperthermia in rats. These findings suggest that DOI-induced hyperthermia in rats is mediated by stimulation of 5-HT_2A receptors.