Repeated administration of the 5-HT₁B/₁A agonist, RU 24969, facilitates the acquisition of MDMA self-administration: role of 5-HT₁A and 5-HT₁B receptor mechanisms.
Dane Aronsen, Natasha Bukholt, Susan Schenk
Psychopharmacology April 2016 DOI: 10.1007/s00213-016-4225-x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical behavioral pharmacology study Peer reviewed |
|---|---|
| Population | Animals (species not specified) |
| Interventions | RU 24969 MDMA |
| Dose | RU 24969 0.0 or 3.0 mg/kg, twice daily (bid) |
| Duration | 3-day pretreatment phase |
| Topics | MDMA Serotonin |
| Keywords | 5-ht1a 5-ht1b Acquisition Dopamine Ru 24969 Self-administration |
| Key points | Repeated administration of the 5-HT1B/1A receptor agonist RU 24969 (3.0 mg/kg, twice daily for 3 days) significantly decreased the latency to acquire MDMA self-administration and increased the proportion of animals that acquired it. Rightward shifts in dose-effect curves for 8-OH-DPAT-induced hyperactivity and RU 24969-induced adipsia suggested desensitization of 5-HT1A and 5-HT1B receptors. The authors suggest that initial reinforcing effects of MDMA are modulated by these receptor mechanisms. |
Abstract
3,4 Methylenedioxymethamphetamine (MDMA) preferentially stimulates the release of serotonin (5-HT) that subsequently produces behavioral responses by activation of post-synaptic receptor mechanisms. The 5-HT1A and 5-HT1B receptors are both well localized to regulate dopamine (DA) release, and have been implicated in modulating the reinforcing effects of many drugs of abuse, but a role in acquisition of self-administration has not been determined. This study was designed to determine the effect of pharmacological manipulation of 5-HT1A and 5-HT1B receptor mechanisms on the acquisition of MDMA self-administration. The 5-HT1B/1A receptor agonist, RU 24969 (0.0 or 3.0 mg/kg, bid), was administered for 3 days in order to down-regulate both 5-HT1A and 5-HT1B receptors. Following the pretreatment phase, latency to acquisition of MDMA self-administration was measured. Repeated administration of RU 24969 significantly decreased the latency to acquisition and increased the proportion of animals that acquired MDMA self-administration. Dose-effect curves for the 5-HT1A-mediated hyperactivity produced by the 5-HT1A agonist, 8-OH-DPAT, and the 5-HT1B-mediated adipsic response produced by RU 24969 were shifted rightward, suggesting a desensitization of 5-HT1A and 5-HT1B receptor mechanisms. These data suggest that the initial reinforcing effects of MDMA are modulated by 5-HT1A and/or 5-HT1B receptor mechanisms. The potential impact of these changes on the DAergic response relevant to self-administration and a possible role in conditioned reinforcement pertaining to acquisition of self-administration are discussed.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 3
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- Comparison of the effects of abstinence on MDMA and cocaine self-administration in rats. Psychopharmacology November 2018
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and 6 more in the library