Aims: 

In studies of the beta3-adrenoceptor antagonist SR59230A, it has beenreported that the hyperthermia to MDMA involves beta3- in addition toalpha1-adrenoceptors in rats (Sprague et al., 2004). In this study, we wishedto investigate the actions of SR59230A on temperature responses to MDMAin mice.

Methods: 

C57-BL/6 WT mice (22-30g male) were implanted underether anaesthesia with intra-abdominal temperature probes (DSI). After 14days, temperature was recorded in freely moving mice by telemetry. Drugswere injected subcutaneously. Statistical comparisons were carried out usingANOVA with post tests, as appropriate.

Results: 

MDMA (20 mg/kg) produceda significant hyperthermia beginning at approximately 100 min after injection.Prazosin (0.1mg/kg) or SR59230A (5 mg/kg), or the combination of prazosinand SR59230A, produced essentially similar effects: the response to MDMA wasaltered from a monophasic hyperthermia to a biphasic hypothermia followedby hyperthermia (e.g. MDMA produced initial decreases of 1.94 ± 0.45°C and 1.96 ± 0.31°C in the presence of prazosin or SR59230A, respectively). Selective alpha1A- or alpha1D-adrenoceptor antagonists when given alone did not affect the hyperthermia to MDMA, but in combination acted like prazosin, revealing an initial hypothermia to MDMA. However, SR59230A also has potency as an antagonist at alpha1A-, alpha1B- and alpha1D-adrenoceptors in functional and ligand binding studies in vitro.

Conclusion: 

The beta3-adrenoceptor antagonist SR59230A reduced hyperthermic actions of MDMA in mice, but we cannot rule out alpha1-adrenoceptor antagonist actions. Sprague, J.E. et al. (2004). Br. J. Pharmacol. 142, 667-670.

Supported by the Health Research Board (Ireland).