PMID- 31173919 OWN - NLM STAT- MEDLINE DCOM- 20200402 LR - 20200901 IS - 1095-9564 (Electronic) IS - 1074-7427 (Print) IS - 1074-7427 (Linking) VI - 163 DP - 2019 Sep TI - Neuroplasticity transcript profile of the ventral striatum in the extinction of opioid-induced conditioned place preference. PG - 107031 LID - S1074-7427(19)30098-X [pii] LID - 10.1016/j.nlm.2019.107031 [doi] AB - Persistent drug-seeking behavior has been associated with deficits in neural circuits that regulate the extinction of addictive behaviors. Although there is extensive data that associates addiction phases with neuroplasticity changes in the reward circuit, little is known about the underlying mechanisms of extinction learning of opioid associated cues. Here, we combined morphine-conditioned place preference (CPP) with real-time polymerase chain reaction (RT-PCR) to identify the effects of extinction training on the expression of genes (mRNAs) associated with synaptic plasticity and opioid receptors in the ventral striatum/nucleus accumbens (VS/NAc). Following morphine extinction training, we identified two animal subgroups showing either extinction (low CPP) or extinction-resistance (high CPP). A third group were conditioned to morphine but did not receive extinction training (sham-extinction; high CPP). RT-PCR results showed that brain derived neurotrophic factor (Bdnf) was upregulated in rats showing successful extinction. Conversely, the lack of extinction training (sham-extinction) upregulated genes associated with kinases (Camk2g), neurotrophins (Ngfr), synaptic connectivity factors (Ephb2), glutamate neurotransmission (Grm8) and opioid receptors (mu1, Delta1). To further identify genes modulated by morphine itself, comparisons with their saline-counterparts were performed. Results revealed that Bdnf was consistently upregulated in the extinction group. Alternatively, widespread gene modulation was observed in the group with lack of extinction training (i.e. Drd2, Cnr1, Creb, mu1, Delta1) and the group showing extinction resistance (i.e. Crem, Rheb, Tnfa). Together, our study builds on the identification of putative genetic markers for the extinction learning of drug-associated cues. CI - Published by Elsevier Inc. FAU - Martinez-Rivera, Freddyson J AU - Martinez-Rivera FJ AD - Department of Anatomy and Neurobiology, School of Medicine, Medical Sciences Campus, University of Puerto Rico, San Juan, PR 00936, USA. FAU - Martinez, Namyr A AU - Martinez NA AD - Department of Physiology and Biophysics, School of Medicine, Medical Sciences Campus, University of Puerto Rico, San Juan, PR 00936, USA; Molecular Sciences Building, University of Puerto Rico, San Juan, PR 00926, USA. FAU - Martinez, Magdiel AU - Martinez M AD - Department of Physiology and Biophysics, School of Medicine, Medical Sciences Campus, University of Puerto Rico, San Juan, PR 00936, USA; Molecular Sciences Building, University of Puerto Rico, San Juan, PR 00926, USA. FAU - Ayala-Pagan, Roxsana N AU - Ayala-Pagan RN AD - Department of Anatomy and Neurobiology, School of Medicine, Medical Sciences Campus, University of Puerto Rico, San Juan, PR 00936, USA. FAU - Silva, Walter I AU - Silva WI AD - Department of Physiology and Biophysics, School of Medicine, Medical Sciences Campus, University of Puerto Rico, San Juan, PR 00936, USA; Molecular Sciences Building, University of Puerto Rico, San Juan, PR 00926, USA. FAU - Barreto-Estrada, Jennifer L AU - Barreto-Estrada JL AD - Department of Anatomy and Neurobiology, School of Medicine, Medical Sciences Campus, University of Puerto Rico, San Juan, PR 00936, USA. Electronic address: jennifer.barreto1@upr.edu. LA - eng GR - SC2 DA047809/DA/NIDA NIH HHS/United States GR - U54 MD007600/MD/NIMHD NIH HHS/United States GR - R25 GM061838/GM/NIGMS NIH HHS/United States GR - G12 RR003051/RR/NCRR NIH HHS/United States GR - G12 MD007600/MD/NIMHD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20190604 PL - United States TA - Neurobiol Learn Mem JT - Neurobiology of learning and memory JID - 9508166 RN - 0 (Analgesics, Opioid) RN - 0 (Receptors, Opioid) RN - 76I7G6D29C (Morphine) SB - IM MH - Analgesics, Opioid/*pharmacology MH - Animals MH - Conditioning, Classical/*drug effects MH - Extinction, Psychological MH - Male MH - Morphine/*pharmacology MH - Neuronal Plasticity/*drug effects MH - Nucleus Accumbens/drug effects/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Real-Time Polymerase Chain Reaction MH - Receptors, Opioid/drug effects/metabolism MH - Transcriptome/drug effects MH - Ventral Striatum/*drug effects/metabolism PMC - PMC6689252 MID - NIHMS1532181 OTO - NOTNLM OT - Bdnf OT - Conditioned place preference OT - Genes OT - Learning OT - Morphine OT - Reward COIS- Financial disclosures The authors reported no biomedical financial interests or potential conflicts of interest. EDAT- 2019/06/08 06:00 MHDA- 2020/04/03 06:00 PMCR- 2020/09/01 CRDT- 2019/06/08 06:00 PHST- 2018/12/21 00:00 [received] PHST- 2019/05/27 00:00 [revised] PHST- 2019/06/03 00:00 [accepted] PHST- 2019/06/08 06:00 [pubmed] PHST- 2020/04/03 06:00 [medline] PHST- 2019/06/08 06:00 [entrez] PHST- 2020/09/01 00:00 [pmc-release] AID - S1074-7427(19)30098-X [pii] AID - 10.1016/j.nlm.2019.107031 [doi] PST - ppublish SO - Neurobiol Learn Mem. 2019 Sep;163:107031. doi: 10.1016/j.nlm.2019.107031. Epub 2019 Jun 4.