Tolerance to the locomotor-activating effects of 3,4-methylenedioxymethamphetamine (MDMA) predicts escalation of MDMA self-administration and cue-induced reinstatement of MDMA seeking in rats.
Kevin T. Ball, Mylissa Slane
Behavioural Brain Research November 1, 2014 DOI: 10.1016/j.bbr.2014.08.010 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical observational study using the self-administration-extinction-reinstatement model Peer reviewed |
|---|---|
| Population | Rats a priori characterized for locomotor sensitization or tolerance to MDMA |
| Intervention | MDMA |
| Topics | MDMA |
| Keywords | Cue Reinstatement Self-administration Sensitization Tolerance |
| Key findings | Rats that developed tolerance to MDMA's locomotor-activating effects showed escalated MDMA self-administration and cue-induced reinstatement of MDMA seeking, whereas rats that developed sensitization maintained stable self-administration and showed no cue-induced reinstatement. The authors argue these individual differences in psychomotor response reliably predict addiction-like behaviors in rats. |
Abstract
Pre-clinical studies of individual differences in addiction vulnerability have been increasing over recent years, but the amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) has received relatively little attention in this regard. Previously, we reported large individual differences both in rats' initial behavioral response to experimenter-administered MDMA and their degree of behavioral sensitization to repeated administration. To determine whether these differences could predict subsequent patterns of MDMA-taking or -seeking behaviors we used the self-administration-extinction-reinstatement model to examine addiction-like behavior (i.e., escalation of MDMA self-administration and cue-induced reinstatement of MDMA seeking) in rats a priori characterized for either locomotor sensitization or tolerance to MDMA. Rats that developed tolerance to the locomotor-activating effects of MDMA had a significantly larger locomotor response to the first MDMA injection relative to rats that developed sensitization. Importantly, rats that developed tolerance subsequently displayed an escalation of MDMA self-administration over days, as well as clear cue-induced reinstatement of MDMA seeking following extinction. Conversely, rats that developed locomotor sensitization to MDMA subsequently maintained relatively stable levels of MDMA self-administration over days and showed no cue-induced reinstatement of MDMA seeking. These results show that differences in the level of psychomotor activation following acute and repeated MDMA administration can reliably predict two important addiction-like behaviors in rats, which may have implications in the prediction of compulsive MDMA use in humans.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
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- The entactogen MDMA (3,4-methylenedioxymethamphetamine, "Ecstasy") disrupts helping behaviour while reinforcing electrophysiological indicators of potentially associated synaptic plasticity in male Sprague-Dawley rats. Frontiers in Pharmacology 2026
- The serotonin 5-HT2C receptor and the non-addictive nature of classic hallucinogens. Journal of Psychopharmacology November 15, 2016
- Serotonin antagonists fail to alter MDMA self-administration in rats. Pharmacology, Biochemistry, and Behavior September 2016
and 2 more in the library
Cites 6
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- Is ecstasy a drug of dependence? Drug and Alcohol Dependence February 1, 2010
and 1 more in the library