Yohimbine reinstates extinguished 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) seeking in rats with prior exposure to chronic yohimbine.
Kevin T. Ball, Hanna Jarsocrak, Johanna Hyacinthe, Justina Lambert, James Lockowitz, Jordan Schrock
Behavioural Brain Research November 1, 2015 DOI: 10.1016/j.bbr.2015.07.056 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical behavioral pharmacology study (rat self-administration and reinstatement experiment) Peer reviewed |
|---|---|
| Population | Rats with a history of MDMA self-administration (0.50 mg/kg/infusion) or food self-administration |
| Interventions | MDMA Yohimbine SCH-23390 food self-administration |
| Dose | MDMA 0.50 mg/kg/infusion; acute yohimbine 2.0 mg/kg; chronic yohimbine 5.0 mg/kg × 10 days; SCH-23390 0.0 or 10.0 μg/kg |
| Duration | Chronic yohimbine injections for 10 days prior to reinstatement tests |
| Topics | MDMA |
| Keywords | Dopamine Reinstatement Sch-23390 Stress Yohimbine |
| Key findings | Acute yohimbine reinstated extinguished MDMA and food seeking only in rats with prior chronic yohimbine exposure, indicating that chronic stress sensitizes subsequent stress-induced reinstatement. SCH-23390 blocked this potentiation for food seeking but not MDMA seeking, suggesting the mechanisms linking chronic stress to relapse differ by drug use history. |
Abstract
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.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 3
- Regional changes in ∆FosB expression in rat brain following MDMA self‐administration predict increased sensitivity to effects of locally infused MDMA Addiction Biology September 1, 2020
- Predicting the Abuse Liability of Entactogen-Class, New and Emerging Psychoactive Substances via Preclinical Models of Drug Self-administration. Current Topics in Behavioral Neurosciences 2017
- Neurochemical substrates of the rewarding effects of MDMA: implications for the development of pharmacotherapies to MDMA dependence. Behavioural Pharmacology April 2016
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