The role of dopamine D1 receptors in MDMA-induced memory impairments
Hanna Squire, Jiun Youn, Bart A. Ellenbroek, David N. Harper
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial |
|---|---|
| Population | Adult male Wistar DAD1-/- rats and wild type control rats |
| Interventions | MDMA saline |
| Dose | 1.5, 2.25 and 3 mg/kg |
| Duration | 25 training sessions; testing occurred over three blocks of MDMA administration, with each subject receiving all drug doses and saline three times |
| Topics | MDMA |
| Key findings | Control rats showed decreased accuracy on a spatial working memory task after 2.25 and 3 mg/kg MDMA during the third block of administration, driven by increased perseverative errors, while DAD1-/- rats with reduced D1 receptor function were protected from these deficits. The authors argue that acute MDMA impairs memory in rats via D1 receptor overstimulation rather than predominantly serotonergic mechanisms. |
Abstract
(±) 3,4-methylenedioxymethamphetamine (MDMA) is a recreationally abused psychostimulant that impairs memory performance. This effect is often attributed to a working memory impairment resulting from compromised serotonin systems. However, recent evidence from non-human animal experimental studies suggests that acute MDMA may indirectly impair memory performance through overstimulation of dopamine (DA) D1 receptors, which increases perseverative responding during memory tasks. This hypothesis was explored using DA D1 mutant (DAD1-/-) rats which possess a selective down-regulation in functional D1 receptors. Adult male Wistar DAD1-/- rats and wild type controls were trained over 25 sessions on a spatial working memory T-maze task, delayed non-matching to position (DNMTP). Once trained, the rats were administered MDMA (1.5, 2.25 and 3 mg/kg) or saline fifteen minutes prior to testing on DNMTP with all subjects experiencing all drug doses and saline three times. We predicted that controls would demonstrate decreased task accuracy following MDMA, driven by an increase in perseverative errors. In contrast, we predicted that DAD1-/- rats would be protected from MDMA-induced perseverative errors due to their reduced D1 receptor function. As predicted, during the third block of MDMA administration, control rats demonstrated decreased task accuracy following 2.25 and 3 mg/kg doses, driven by an increase in perseverative errors. In addition, DAD1-/- rats were protected from MDMA-induced task deficits. These findings challenge the assumption that MDMA’s acute effects on memory performance are predominantly due to serotonergic mechanisms and provide support for the hypothesis that acute MDMA impairs memory performance in rats via overstimulation of D1 receptors by increasing perseverative behaviour.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cites 13
- Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Journal of Pharmacology and Experimental Therapeutics 1987
- 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Journal of Pharmacology and Experimental Therapeutics September 1, 1987
- 3,4‐Methylenedioxymethamphetamine (MDMA, “Ecstasy”): pharmacology and toxicology in animals and humans Addiction May 1, 1994
- 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings Psychopharmacology March 15, 2006
- Transient memory impairment after acute dose of 75mg 3.4-Methylene-dioxymethamphetamine Journal of Psychopharmacology November 1, 2005
and 8 more in the library