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. 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. 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). 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. 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.
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Document Type: Research Article
Publication date: October 1, 2013