Yohimbine reinstates extinguished 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) seeking in rats with prior exposure to chronic yohimbine.

Although exposure to acute stress has been shown to reinstate extinguished responding for a wide variety of drugs, no studies have investigated stress-induced reinstatement in animals with a history of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) self-administration. Thus, rats were trained to press a lever for MDMA (0.50 mg/kg/infusion) in daily sessions, and lever pressing was subsequently extinguished in the absence of MDMA and conditioned cues (light and tone). We then tested the ability of acute yohimbine (2.0 mg/kg), a pharmacological stressor, to reinstate lever-pressing under extinction conditions. Additionally, to model chronic stress, some rats were injected daily with yohimbine (5.0 mg/kg × 10 days) prior to reinstatement tests. To assess dopaminergic involvement, chronic yohimbine injections were combined with injections of SCH-23390 (0.0 or 10.0 μg/kg), a dopamine D1-like receptor antagonist. In a separate experiment, rats with a history of food self-administration were treated and tested in the same way. Results showed that acute yohimbine injections reinstated extinguished MDMA and food seeking, but only in rats with a history of chronic yohimbine exposure. Co-administration of SCH-23390 with chronic yohimbine injections prevented the potentiation of subsequent food seeking, but not MDMA seeking. These results suggest that abstinent MDMA users who also are exposed to chronic stress may be at increased risk for future relapse, and also that the effects of chronic stress on relapse may be mediated by different mechanisms depending on one's drug use history.