Alpha1-adrenergic receptors mediate the locomotor response to systemic administration of (+/-)-3,4-methylenedioxymethamphetamine (MDMA) in rats

The recreational drug 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) increases locomotor activity when administered to rats. Although the published pharmacology of MDMA has focused almost exclusively on the roles of serotonin and dopamine, in vitro studies indicate that MDMA induces serotonin and norepinephrine release with equal potency. The present experiments tested the hypothesis that blockade of alpha(1)-adrenoceptors with systemic or local administration of the antagonist prazosin would attenuate the locomotor response to systemic administration of (+/-)-MDMA. Pretreatment with systemic prazosin (0.5 mg/kg) or microinjections into either the prefrontal cortex or ventral tegmental area completely blocked the locomotor stimulant effects of 5 mg/kg (+/-)-MDMA, assessed using a computerized Behavioral Pattern Monitor. Prazosin was more potent in blocking the locomotor stimulant effects of (+/-)-MDMA than a 2 mg/kg dose of (+)-amphetamine that produced a similar locomotor activity increase. These results indicate that activation of alpha(1)-adrenoceptors in both the prefrontal cortex and ventral tegmental areas modulates the locomotor response to MDMA.