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Updated: Aug 6, 2026
Three Laboratory Procedures for Assessing Different Manifestations of Impulsivity in Rats
Published on: March 17, 2019
High-dose MDMA does not result in long-term changes in impulsivity in the rat
Kathryn S Saadat1, J Martin Elliott, A Richard Green
1Neuropharmacology Research Group, School of Pharmacy, De Monfort University, The Gateway, Leicester, LE1 9BH, UK.
Rationale:
Evidence suggests that recreational users of (+/-)3,4-methylenedioxymethamphetamine HCl (MDMA, "ecstasy") have cognitive and behavioral deficits and show increased impulsivity consistent with 5-hydroxytryptamine (5-HT) neurotoxicity. MDMA effects on impulsivity in users are difficult to establish being confounded by polydrug use and individual predisposition to impulsivity or behavioral inhibition.
Objective:
We previously observed a long-term anxiolytic effect of a neurotoxic dose of MDMA on elevated plus maze behavior in Dark Agouti (DA) rats while other strains were reported to show anxiogenesis. We have now examined whether MDMA influences impulsivity producing disinhibited behavior interpretable as anxiolysis.
Methods:
Impulsivity was measured using an operant visuospatial discrimination procedure. Male DA rats (n = 24) were trained to lever press for food reward in response to a light-stimulus and subsequently required to withhold responding. Correct responses, premature responses, and response latencies were used as measures of accuracy and impulsivity. Trained rats were administered MDMA (5 mg/kg, i.p. at 3-h intervals to a total of three injections). Performance was measured at 3 h and 7, 27, 49, and 80 days posttreatment.
Results:
There was a short-term effect of MDMA on the percentage of correct responses at 3 h and day 1 with recovery to control levels by days 7-8 and no significant long-term changes up to day 80. There was no effect of MDMA on premature responses on any of the days measured. MDMA reduced cortical 5-HT content (MDMA 363 +/- 14 ng/g and control 440 +/- 10 ng/g tissue).
Conclusion:
These results suggest that impulsivity may not be directly altered by MDMA despite serotonergic neurotoxicity.
Insights
MDMA (ecstasy) causes neurotoxicity but does not appear to directly increase impulsivity in rats, even with long-term effects. This study investigated MDMA
Area of Science:
- Neuroscience
- Psychopharmacology
Background:
- Recreational (+/-)3,4-methylenedioxymethamphetamine HCl (MDMA, "ecstasy") use is linked to cognitive deficits and impulsivity, potentially due to 5-hydroxytryptamine (5-HT) neurotoxicity.
- Previous research noted long-term anxiolytic effects of MDMA in Dark Agouti (DA) rats, contrasting with anxiogenesis in other strains.
Purpose of the Study:
- To investigate whether MDMA influences impulsivity and produces disinhibited behavior in DA rats.
- To determine if MDMA-induced serotonergic neurotoxicity correlates with behavioral changes in impulsivity.
Main Methods:
- Male DA rats were trained on an operant visuospatial discrimination task measuring accuracy and impulsivity.
- Rats received MDMA (5 mg/kg) via intraperitoneal injection, with performance assessed at multiple time points up to 80 days post-treatment.
- Cortical 5-HT content was measured post-treatment.
Main Results:
- MDMA caused a short-term decrease in response accuracy at 3 hours and 1 day, with recovery by days 7-8.
- No significant long-term changes in accuracy or premature responses (impulsivity) were observed up to 80 days.
- MDMA significantly reduced cortical 5-HT content, confirming neurotoxic effects.
Conclusions:
- MDMA-induced serotonergic neurotoxicity in DA rats did not lead to lasting alterations in impulsivity.
- These findings suggest that impulsivity may not be a direct behavioral consequence of MDMA neurotoxicity.
