PUBLICATION

Increased Response to 3,4-Methylenedioxymethamphetamine (MDMA) Reward and Altered Gene Expression in Zebrafish During Short- and Long-Term Nicotine Withdrawal

Authors
Ponzoni, L., Teh, M.T., Torres-Perez, J.V., Brennan, C.H., Braida, D., Sala, M.
ID
ZDB-PUB-201126-6
Date
2020
Source
Molecular neurobiology   58(4): 1650-1663 (Journal)
Registered Authors
Brennan, Caroline
Keywords
Conditioned place preference, Psychostimulants, Receptors, Reward
MeSH Terms
  • Animals
  • Conditioning, Classical
  • Female
  • Gene Expression Regulation*/drug effects
  • Male
  • N-Methyl-3,4-methylenedioxyamphetamine/pharmacology*
  • Nicotine/adverse effects*
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Receptors, Dopamine/genetics
  • Receptors, Dopamine/metabolism
  • Receptors, Oxytocin/genetics
  • Receptors, Oxytocin/metabolism
  • Receptors, Purinergic P1/genetics
  • Receptors, Purinergic P1/metabolism
  • Reward*
  • Substance Withdrawal Syndrome/genetics*
  • Swimming
  • Time Factors
  • Zebrafish/genetics*
PubMed
33236326 Full text @ Mol. Neurobiol.
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.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping