Increased response to 3,4 methylenedioxymethamphetamine (MDMA) reward and altered gene expression in zebrafish during short- and long-term nicotine withdrawal
Luisa Ponzoni, M. Teh, J. V. Torres-Pérez, C. Brennan, Daniela Braida, M. Sala
Molecular Neurobiology November 24, 2020 DOI: 10.1007/s12035-020-02225-5 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Adult zebrafish, drug-treated and control |
| Interventions | Nicotine MDMA |
| Dose | 0.1 mg/kg MDMA; 2-week nicotine exposure (dose not stated) |
| Duration | 2-week nicotine exposure followed by 2–60 days of withdrawal |
| Measures | Conditioned place preference (CPP), quantitative real-time PCR of mRNA |
| Topics | MDMA |
| Key findings | Zebrafish pre-exposed to nicotine for two weeks showed increased conditioned place preference to low-dose MDMA (0.1 mg/kg) at 2, 7, 30, and 60 days of withdrawal compared with un-exposed fish. Nicotine withdrawal and MDMA-induced CPP were associated with altered brain expression of c-Fos, vasopressin, oxytocin, D3 dopaminergic receptor, p35, and α4 genes. The authors suggest these gene alterations could account for the altered sensitivity to MDMA's rewarding effects during nicotine withdrawal. |
Abstract
An interactive effect between nicotine and 3,4-methylenedioxymethamphetamine (MDMA) has been reported but the mechanism underlying such interaction is not completely understood. This study used zebrafish to explore gene expression changes associated with altered sensitivity to the rewarding effects of MDMA following 2-week exposure to nicotine and 2–60 days of nicotine withdrawal. Reward responses to MDMA were assessed using a conditioned place preference (CPP) paradigm and gene expression was evaluated using quantitative real-time PCR of mRNA from whole brain samples from drug-treated and control adult zebrafish. Zebrafish pre-exposed for 2 weeks to nicotine showed increased conditioned place preference in response to low-dose, 0.1 mg/kg, MDMA compared to un-exposed fish at 2, 7, 30 and 60 days withdrawal. Pre-exposure to nicotine for 2 weeks induced a significant increase of c-Fos and vasopressin receptor expression but a decrease of D3 dopaminergic and oxytocin receptor expression at 2 days of withdrawal. C-Fos mRNA increased also at 7, 30, 60 days of withdrawal. Nicotine pre-exposed zebrafish submitted to MDMA-induced CPP showed an increase in expression of p35 at day 2, α4 at day 30, vasopressin at day 7 and D3 dopaminergic receptor at day 7, 30 and 60. These gene alterations could account for the altered sensitivity to the rewarding effects of MDMA in nicotine pre-exposed fish, suggesting that zebrafish have an altered ability to modulate behaviour as a function of reward during nicotine withdrawal.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 2
- Exploring the impact of MDMA and oxytocin ligands on anxiety and social responses: A comprehensive behavioural and molecular study in the zebrafish model. Journal of Psychopharmacology April 1, 2025
- Unveil the toxicity induced on early life stages of zebrafish (Danio rerio) exposed to 3,4-methylenedioxymethamphetamine (MDMA) and its enantiomers. The Science of the total environment December 10, 2024
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and 3 more in the library