Acquisition of MDMA self‐administration: pharmacokinetic factors and MDMA‐induced serotonin release
Sarah Bradbury, Judith Bird, Joyce Colussi‐mas, Melanie Mueller, George A. Ricaurte, Susan Schenk
Addiction Biology June 14, 2013 DOI: 10.1111/adb.12069 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | MDMA 5 7-dihydroxytryptamine (5 |
| Dose | 1.0 mg/kg MDMA (iv) for PK profiles; 1.0 and 3.0 mg/kg MDMA (iv) for microdialysis |
| Topics | MDMA Serotonin |
| Keywords | Pharmacology Pharmacokinetics |
| Citations | 59 |
| Key findings | Serotonin limits the initial sensitivity to the positively reinforcing effects of MDMA and delays the acquisition of reliable self-administration. |
Abstract
Abstract The current study aimed to elucidate the role of pharmacokinetic ( PK ) parameters and neurotransmitter efflux in explaining variability in (±) 3, 4‐methylenedioxymethamphetamine ( MDMA ) self‐administration in rats. PK profiles of MDMA and its major metabolites were determined after the administration of 1.0 mg/kg MDMA (iv) prior to, and following, the acquisition of MDMA self‐administration. Synaptic levels of 5‐hydroxytryptamine ( 5HT ) and dopamine ( DA ) in the nucleus accumbens were measured following administration of MDMA (1.0 and 3.0 mg/kg, iv) using in vivo microdialysis and compared for rats that acquired or failed to acquire MDMA self‐administration. Effects of the 5HT neurotoxin, 5,7 dihydroxytryptamine (5, 7‐ DHT ), on the acquisition of MDMA and cocaine self‐administration were also determined. In keeping with previous findings, approximately 50% of rats failed to meet a criterion for acquisition of MDMA self‐administration. The PK profiles of MDMA and its metabolites did not differ between rats that acquired or failed to acquire MDMA self‐administration. MDMA produced more overflow of 5HT than DA . The MDMA ‐induced 5HT overflow was lower in rats that acquired MDMA self‐administration compared with those that did not acquire self‐administration. In contrast, MDMA ‐induced DA overflow was comparable for the two groups. Prior 5,7‐ DHT lesions reduced tissue levels of 5HT and markedly increased the percentage of rats that acquired MDMA self‐administration and also decreased the latency to acquisition of cocaine self‐administration. These data suggest that 5HT limits the initial sensitivity to the positively reinforcing effects of MDMA and delays the acquisition of reliable self‐administration.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 23
- REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics Pharmacological Reviews June 20, 2019
- The Effects of Acutely Administered 3,4-Methylenedioxymethamphetamine on Spontaneous Brain Function in Healthy Volunteers Measured with Arterial Spin Labeling and Blood Oxygen Level–Dependent Resting State Functional Connectivity Biological Psychiatry January 10, 2014
- Receptor-Enriched Analysis of functional connectivity by targets (REACT): A novel, multimodal analytical approach informed by PET to study the pharmacodynamic response of the brain under MDMA Neuroimage April 4, 2019
- Altered Insula Connectivity under MDMA. Neuropsychopharmacology February 14, 2017
- Methylenedioxymethamphetamine (MDMA): Serotonergic and dopaminergic mechanisms related to its use and misuse Journal of Neurochemistry March 12, 2021
and 18 more in the library
Cites 17
- Recreational MDMA use in Sydney: a profile of ‘Ecstasy’ users and their experiences with the drug British Journal of Addiction August 1, 1992
- MDMA self‐administration in rats: acquisition, progressive ratio responding and serotonin transporter binding European Journal of Neuroscience November 16, 2007
- Reinforcing Effects of MDMA (‘Ecstasy’) in Drug-Naive and Cocaine-Trained Rats Pharmacology 2001
- MDMA Self-Administration in Laboratory Animals: A Summary of the Literature and Proposal for Future Research Neuropsychobiology 2009
- Dopaminergic mechanisms of reinstatement of MDMA‐seeking behaviour in rats British Journal of Pharmacology December 30, 2010
and 12 more in the library