Influence of ketanserin on the effects of methylenedioxymethamphetamine on body temperature in the mouse

1. We have investigated the ability of the 5HT₂-receptor antagonist ketanserin to affect the hyperthermia produced by methylenedioxymethamphetamine (MDMA) in conscious mice and examined whether α₁-adrenoceptor antagonist actions are involved.
2. Mice were implanted with intra-abdominal temperature probes under anaesthesia and allowed 2 weeks recovery. MDMA (20 mg kg⁻¹) was administered subcutaneously 30 min after vehicle or test antagonist and effects on body temperature monitored by telemetry.
3. Following vehicle, MDMA produced a slowly developing hyperthermia, reaching a maximum increase of 1.24 °C at 150 min postinjection. Ketanserin (0.5 mg kg⁻¹) revealed a significant and marked early hypothermia to MDMA, an effect that is mimicked by the α₁-adrenoceptor antagonist prazosin (0.1 mg kg⁻¹).
4. Functional studies revealed antagonist actions of ketanserin at α₁-adrenoceptors in rat aorta and rat vas deferens in vitro indicative of α₁-adrenoceptor antagonist actions at the concentration used in vivo.
5. In conclusion, ketanserin (0.5 mg kg⁻¹) modulates the hyperthermic actions of MDMA in mice. Although we cannot rule out additional actions at 5HT₂-receptors, the actions of ketanserin are consistent with α₁-adrenoceptor antagonism. There is no clear evidence from this study that 5HT₂-receptors mediate the hyperthermic response to MDMA.