Increased Response to 3,4-Methylenedioxymethamphetamine (MDMA) Reward and Altered Gene Expression in Zebrafish During Sh
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Increased Response to 3,4-Methylenedioxymethamphetamine (MDMA) Reward and Altered Gene Expression in Zebrafish During Short- and Long-Term Nicotine Withdrawal Luisa Ponzoni 1 & Muy-Teck Teh 2 Mariaelvina Sala 4
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Jose V. Torres-Perez 3
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Caroline H. Brennan 3
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Daniela Braida 1
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Received: 12 August 2020 / Accepted: 19 November 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
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 preexposed 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. Keywords Psychostimulants . Conditioned place preference . Reward . Receptors
Introduction Nicotine is the main psychoactive substance contained in cigarette smoke and is able to cause both physical and psychological dependence. As with other addictive drugs, nicotine acts on the brain’s reward circuit to cause dopamine release in the nucleus accumbens (NAc) [1]. Smoking behaviour and psychostimulant use are highly comorbid [2]. Compared to the general population, psychostimulant users report extremely * Mariaelvina Sala [email protected] 1
Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, Milan, Italy
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Centre for Oral Immunobiology and Regenerative Medicine, Institute of Dentistry, Barts & The London School of Medicine and Dentistry, Queen Mary University of London, England, UK
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School of Biological and Chemical Sciences, Queen Mary University of London, London, UK
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Neuroscience Institute, CNR, Via Vanvitelli 32, 20129 Milan, Italy
high rates of cigarette smoking usage [3, 4]. Indeed, tobacco use occurs in about 90% of methamphetamin
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