Repeated MDMA administration increases MDMA-produced locomotor activity and facilitates the acquisition of MDMA self-administration: role of dopamine D2 receptor mechanisms.
Ross Van de Wetering, Susan Schenk
Psychopharmacology February 10, 2017 DOI: 10.1007/s00213-017-4554-4 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Population | Male Sprague-Dawley rats |
| Interventions | MDMA Eticlopride |
| Dose | MDMA 10.0 mg/kg (pretreatment), MDMA 5 mg/kg (test), eticlopride 0.3 mg/kg |
| Duration | Five-day pretreatment regimen; testing two days after the final session |
| Topics | MDMA |
| Keywords | Animals Rats, sprague-dawley Salicylamides N-methyl-3,4-methylenedioxyamphetamine Receptors, dopamine d2 Dopamine antagonists Serotonin agents Self administration Motor activity Locomotion Dose-response relationship, drug Male Dopamine receptor Sensitization Self-administration Eticlopride |
| Key findings | Repeated MDMA pretreatment sensitized both the locomotor-activating and reinforcing effects of MDMA, as shown by enhanced hyperactivity and faster acquisition of self-administration. The D2 antagonist eticlopride blocked sensitization to MDMA-produced hyperactivity but did not significantly alter the facilitated self-administration, leaving the role of D2 receptors in sensitization to MDMA's reinforcing effects equivocal. |
Abstract
Rationale: Repeated exposure to ±3, 4-methylenedioxymethamphetamine (MDMA) produces sensitization to MDMA-produced hyperactivity, but the mechanisms underlying the development of this sensitized response or the relationship to the reinforcing effects of MDMA is unknown.
Objectives: This study determined the effect of a sensitizing regimen of MDMA exposure on the acquisition of MDMA self-administration and investigated the role of dopamine D2 receptor mechanisms.
Methods: Rats received the selective D2 antagonist, eticlopride (0.0 or 0.3 mg/kg, i.p.) and MDMA (0.0 or 10.0 mg/kg, i.p.) during a five-day pretreatment regimen. Two days following the final session, the locomotor activating effects of MDMA (5 mg/kg, i.p.) and the latency to acquisition of MDMA self-administration were determined.
Results: Pretreatment with MDMA enhanced the locomotor activating effects of MDMA and facilitated the acquisition of MDMA self-administration. Administration of eticlopride during MDMA pretreatment completely blocked the development of sensitization to MDMA-produced hyperactivity but failed to significantly alter the facilitated acquisition of MDMA self-administration. Pretreatment with eticlopride alone facilitated the acquisition of self-administration.
Conclusions: These data suggest that repeated MDMA exposure sensitized both the locomotor activating and reinforcing effects of MDMA. Activation of D2 receptors during MDMA pretreatment appears critical for the development of sensitization to MDMA-produced hyperactivity. The role of D2 receptor mechanisms in the development of sensitization to the reinforcing effects of MDMA is equivocal.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
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- 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
- Acute effects of 3,4-methylenedioxymethamphetamine (MDMA) and R(-) MDMA on actigraphy-based daytime activity and sleep parameters in rhesus monkeys. Experimental and Clinical Psychopharmacology June 25, 2018
- Behavioral metabolomics: how behavioral data can guide metabolomics research on neuropsychiatric disorders. Metabolomics : Official journal of the Metabolomic Society August 2, 2023
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