Vascular actions of 3,4-methylenedioxymethamphetamine in α 2A/D-adrenoceptor knockout mice

Abstract

We have investigated the effects of 3,4-methylenedioxymethamphetamine (MDMA) on mean arterial pressure in anaesthetised wild-type and α 2A/D-adrenoceptor knockout mice. In wild-type mice, MDMA (5 mg kg −1) produced a pressor response that declined to baseline by 2 min and fell below baseline to a depressor response by 5 min, whereas MDMA (20 mg kg −1) produced only a pressor response that declined to baseline by 5 min. In wild-type mice, following the injection of the selective α 2A/D-adrenoceptor antagonist, 2-((4,5-dihydro-1 H-imidazole-2-yl)methyl)-2,3-di-hydro-1-methyl-1 H-isoindole (BRL44408), the peak pressor response to MDMA (5 or 20 mg kg −1) was not modified but durations of the pressor effects of both doses of MDMA were prolonged with responses significantly above baseline at 5 min. In α 2A/D-adrenoceptor knockout mice, the peak response to MDMA (5 mg kg −1) was similar to that in wild-type but the response fell to baseline over 5 min with no depressor component, whereas MDMA (20 mg kg −1) produced a sustained pressor response significantly above baseline at 10 min. The responses were similar to those obtained in wild-type in the presence of BRL44408. It is concluded that MDMA produces depressor responses in wild-type mice by action at α 2A/D-adrenoceptors to shorten the duration of the pressor response.