PMID- 33236326 OWN - NLM STAT- MEDLINE DCOM- 20211027 LR - 20220531 IS - 1559-1182 (Electronic) IS - 0893-7648 (Print) IS - 0893-7648 (Linking) VI - 58 IP - 4 DP - 2021 Apr TI - Increased Response to 3,4-Methylenedioxymethamphetamine (MDMA) Reward and Altered Gene Expression in Zebrafish During Short- and Long-Term Nicotine Withdrawal. PG - 1650-1663 LID - 10.1007/s12035-020-02225-5 [doi] AB - 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 D(3) 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, alpha4 at day 30, vasopressin at day 7 and D(3) 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. FAU - Ponzoni, Luisa AU - Ponzoni L AUID- ORCID: 0000-0002-0652-0766 AD - Department of Medical Biotechnology and Translational Medicine, Universita degli Studi di Milano, Milan, Italy. FAU - Teh, Muy-Teck AU - Teh MT AUID- ORCID: 0000-0002-7725-8355 AD - 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. FAU - Torres-Perez, Jose V AU - Torres-Perez JV AUID- ORCID: 0000-0001-6390-9690 AD - School of Biological and Chemical Sciences, Queen Mary University of London, London, UK. FAU - Brennan, Caroline H AU - Brennan CH AUID- ORCID: 0000-0002-4169-4083 AD - School of Biological and Chemical Sciences, Queen Mary University of London, London, UK. FAU - Braida, Daniela AU - Braida D AUID- ORCID: 0000-0002-5867-1902 AD - Department of Medical Biotechnology and Translational Medicine, Universita degli Studi di Milano, Milan, Italy. FAU - Sala, Mariaelvina AU - Sala M AUID- ORCID: 0000-0001-9310-958X AD - Neuroscience Institute, CNR, Via Vanvitelli 32, 20129, Milan, Italy. mariaelvina.sala@unimi.it. LA - eng GR - U01 DA044400/DA/NIDA NIH HHS/United States PT - Journal Article DEP - 20201124 PL - United States TA - Mol Neurobiol JT - Molecular neurobiology JID - 8900963 RN - 0 (RNA, Messenger) RN - 0 (Receptors, Dopamine) RN - 0 (Receptors, Oxytocin) RN - 0 (Receptors, Purinergic P1) RN - 6M3C89ZY6R (Nicotine) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) SB - IM MH - Animals MH - Conditioning, Classical MH - Female MH - *Gene Expression Regulation/drug effects MH - Male MH - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology MH - Nicotine/*adverse effects MH - RNA, Messenger/genetics/metabolism MH - Receptors, Dopamine/genetics/metabolism MH - Receptors, Oxytocin/genetics/metabolism MH - Receptors, Purinergic P1/genetics/metabolism MH - *Reward MH - Substance Withdrawal Syndrome/*genetics MH - Swimming MH - Time Factors MH - Zebrafish/*genetics PMC - PMC8170707 MID - NIHMS1697602 OTO - NOTNLM OT - Conditioned place preference OT - Psychostimulants OT - Receptors OT - Reward COIS- Conflicts of interest The authors declare that they have no conflicts of interest. EDAT- 2020/11/26 06:00 MHDA- 2021/10/28 06:00 PMCR- 2021/06/02 CRDT- 2020/11/25 05:50 PHST- 2020/08/12 00:00 [received] PHST- 2020/11/19 00:00 [accepted] PHST- 2020/11/26 06:00 [pubmed] PHST- 2021/10/28 06:00 [medline] PHST- 2020/11/25 05:50 [entrez] PHST- 2021/06/02 00:00 [pmc-release] AID - 10.1007/s12035-020-02225-5 [pii] AID - 10.1007/s12035-020-02225-5 [doi] PST - ppublish SO - Mol Neurobiol. 2021 Apr;58(4):1650-1663. doi: 10.1007/s12035-020-02225-5. Epub 2020 Nov 24.