The effects of 5 and 20 mg/kg MDMA on mean arterial pressure (MAP) was studied in pentobarbitone-anesthetized wild-type and alpha2A/D receptor knockout (KO) mice. Blood pressure was monitored for 10 min post-MDMA through direct measure of carotid artery. In another study, wild-type and alpha 2A/D KO mice were pre-treated with saline or with the alpha2A/D antagonist 2-((4,5-dihydro-1H-imidazole-2-yl)-methyl)-2,3-dihydro-1-methyl-1H-isoindole (BRL44408). MDMA (5 and 20 mg/kg) increased heart rate in wild-type mice, alpha2A/D knockout mice and wild-type mice given BRL44408. Wild-type mice first exhibited a pressor effect after 5 mg/kg MDMA that returned to baseline after 2 minutes, followed by a depressor effect (compared to saline) at 5 minutes. 20 mg/kg MDMA only produced a pressor effect that returned to baseline at 5 minutes. In alpha2A/D knockout mice, 5 mg/kg MDMA produced a pressor effect that returned to baseline at 5 to 10 minutes, and 20 mg/kg MDMA produced a longer-lasting pressor effect that lasted for at least 10 minutes. Wild-type mice given 1 mg/kg BRL44408 and 5 mg/kg MDMA showed the same pressor response as wild-type mice receiving MDMA alone, except that the pressor response declined slightly at 2 min, and remained above baseline at 10 minutes. When 20 mg/kg MDMA was given to wild-type mice after BR44408, researchers saw a pressor effect lasting for at least 10 minutes. Study findings suggest that MDMA has both alpha1 adrenergic action related to the pressor response (perhaps augmented by 5HT2 activity) and alpha2 adrenoreceptor actions that dampen the pressor response, since absence or antagonism of alpha2 receptors produced a longer-lasting pressor response and eliminated any sign of a depressor effect. The authors propose that recreational doses of MDMA exhibit pressor responses and mask alpha2 adrenoreceptor activity, based on examining rat studies as well as mouse studies. Nevertheless, it is difficult to generalize findings from anesthetized mice to awake, freely moving humans.