Role of α1‐ and β3‐adrenoceptors in the modulation by SR59230A of the effects of MDMA on body temperature in the mouse
Sotiria Bexis, James R. Docherty
British Journal of Pharmacology April 30, 2009 DOI: 10.1111/j.1476-5381.2009.00186.x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Conscious mice |
| Interventions | MDMA SR59230A prazosin |
| Dose | 20 mg/kg MDMA; 0.5 mg/kg and 5 mg/kg SR59230A |
| Duration | 130 minutes post injection |
| Topics | MDMA |
| Keywords | Antagonist Hyperthermia Prazosin Pharmacology |
| Citations | 36 |
| Key findings | SR59230A modulates MDMA-induced hyperthermia in mice primarily through α1-adrenoceptor antagonism, with a low dose slightly attenuating hyperthermia and a high dose unmasking an early hypothermic response. |
Abstract
Background and
Purpose: We have investigated the ability of the β 3 ‐adrenoceptor antagonist 1‐(2‐ethylphenoxy)‐3‐[[(1S)‐1,2,3,4,‐tetrahydro‐1‐naphthalenyl]amino]‐(2S)‐2‐propanol hydrochloride (SR59230A) to affect the hyperthermia produced by methylenedioxymethamphetamine (MDMA) in conscious mice and whether α 1 ‐adrenoceptor antagonist actions are involved. Experimental approach: Mice were implanted with temperature probes under anaesthesia, and allowed 2 week recovery. MDMA (20 mg·kg −1 ) was administered subcutaneously 30 min after vehicle or test antagonist and effects on body temperature monitored by telemetry. Key
Results: Following vehicle, MDMA produced a slowly developing hyperthermia, reaching a maximum increase of 1.8°C at 130 min post injection. A low concentration of SR59230A (0.5 mg·kg −1 ) produced a small but significant attenuation of the slowly developing hyperthermia to MDMA. A high concentration of SR59230A (5 mg·kg −1 ) revealed a significant and marked early hypothermic reaction to MDMA, an effect that was mimicked by the α 1 ‐adrenoceptor antagonist prazosin. Functional and ligand binding studies revealed actions of SR59230A at α 1 ‐adrenoceptors. Conclusions and
Implications: 1‐(2‐ethylphenoxy)‐3‐[[(1S)‐1,2,3,4,‐tetrahydro‐1‐naphthalenyl]amino]‐(2S)‐2‐propanol hydrochloride in high concentrations modulates the hyperthermic actions of MDMA in mice in two ways: by blocking an early α 1 ‐adrenoceptor‐mediated component to reveal a hypothermia, and by a small attenuation of the later hyperthermic component which may possibly be β 3 ‐adrenoceptor‐mediated (this seen with the low concentration of SR59230A). Hence, the major actions of SR59230A in modulating the actions of MDMA on temperature involve α 1 ‐adrenoceptor antagonism.