Involvement of 5-HT2A receptors in MDMA reinforcement and cue-induced reinstatement of MDMA-seeking behaviour
María Juliana Orejarena, Laurence Lanfumey, Rafaël Maldonado, Patricia Robledo
The International Journal of Neuropsychopharmacology October 14, 2010 DOI: 10.1017/s1461145710001215 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study with knockout mice Peer reviewed |
|---|---|
| Population | 5-HT2A receptor knockout mice and wild-type littermates |
| Interventions | MDMA SR46349B (eplivanserin) |
| Dose | MDMA: 0.125 and 0.25 mg/kg per infusion (self-administration); 10 and 20 mg/kg i.p. (locomotion); 20 mg/kg i.p. (dopamine outflow); 5 and 10 mg/kg i.p. (reinstatement). SR46349B: 0.5 mg/kg and 0.25 mg/kg |
| Topics | MDMA Serotonin |
| Keywords | Pharmacology Nucleus accumbens Dopaminergic 5-HT Receptor |
| Citations | 38 |
| Key findings | 5-HT2A receptors are crucial for MDMA-induced reinforcement and cue-induced reinstatement of MDMA-seeking behavior, likely through modulation of mesolimbic dopamine activity. |
Abstract
The serotonergic system appears crucial for (±)-3,4-methylenedioxymethamphetamine (MDMA) reinforcing properties. Current evidence indicates that serotonin 5-HT2A receptors (5-HT2ARs) modulate mesolimbic dopamine (DA) activity and several behavioural responses related to the addictive properties of psychostimulants. This study evaluated the role of 5-HT2ARs in MDMA-induced reinforcement and hyperlocomotion, and the reinstatement of MDMA-seeking behaviour. Basal and MDMA-stimulated extracellular levels of DA in the nucleus accumbens (NAc) and serotonin and noradrenaline in the prefrontal cortex were also assessed. Self-administration of MDMA was blunted in 5-HT2AR knockout (KO) mice compared to wild-type (WT) littermates at both doses tested (0.125 and 0.25 mg/kg per infusion). Horizontal locomotion was increased by MDMA (10 and 20 mg/kg i.p.) to a higher extent in KO than in WT mice. DA outflow in the NAc was lower in KO compared to WT mice under basal conditions and after MDMA (20 mg/kg) challenge. In WT mice, MDMA (5 and 10 mg/kg i.p.) priming did not reinstate MDMA-seeking behaviour, while cue-induced reinstatement was prominent. This cue-induced reinstatement was blocked by administration of the selective 5-HT2AR antagonist, SR46349B (eplivanserin) at a dose of 0.5 mg/kg, but not at 0.25 mg/kg. Our results indicate that 5-HT2ARs are crucial for MDMA-induced reinforcement and cue-induced reinstatement of MDMA-seeking behaviour. These effects are probably due to the modulation of mesolimbic dopaminergic activity.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 21
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- Cognitive Impairment Induced by Delta9-tetrahydrocannabinol Occurs through Heteromers between Cannabinoid CB1 and Serotonin 5-HT2A Receptors PLoS Biology July 9, 2015
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- Methylenedioxymethamphetamine (MDMA): Serotonergic and dopaminergic mechanisms related to its use and misuse Journal of Neurochemistry March 12, 2021
and 16 more in the library
Cites 13
- Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs BMC Pharmacology March 3, 2006
- Human psychopharmacology of Ecstasy (MDMA): a review of 15 years of empirical research Human Psychopharmacology: Clinical and Experimental December 1, 2001
- Transcriptome Fingerprints Distinguish Hallucinogenic and Nonhallucinogenic 5-Hydroxytryptamine 2A Receptor Agonist Effects in Mouse Somatosensory Cortex Journal of Neuroscience October 1, 2003
- 5-HT2 receptors exert a state-dependent regulation of dopaminergic function: studies with MDL 100,907 and the amphetamine analogue, 3,4-methylenedioxymethamphetamine European Journal of Pharmacology November 1, 1992
- Acute Psychological and Neurophysiological Effects of MDMA in Humans Journal of Psychoactive Drugs June 1, 2002
and 8 more in the library