(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.