title: Long-term changes in reward-seeking following morphine withdrawal are associated with altered N-methyl-D-aspartate receptor 1 splice variants in the amygdala.
abstract: The NR1 subunit of the NMDA receptor can be alternatively spliced by the insertion or removal of the N1, C1, C2, or C2' regions. Morphine dependence and withdrawal were previously demonstrated to lower N1 and C2' in the accumbens and lower N1, C1, and C2' in the amygdala (AMY). Withdrawal has also been demonstrated to increase motivational and anxiety/stress behaviors in rats. We tested the hypothesis that NR1 splicing would be associated with these behaviors during an extended withdrawal period of 2 months. Motivation was measured using an operant orofacial assay at non-aversive temperatures (37°C) while anxiety and stress were measured by examining this behavior at aversive temperatures (46°C). Lower C1 and C2 expression levels were observed in the AMY in a subset of the population of withdrawn rats even after 2 months of morphine withdrawal. These subsets were associated with a hypersensitivity to adverse conditions which may reflect long-term alterations in the withdrawn population.
authors.affiliation: Department of Neuroscience, University of Florida College of Medicine, McKnight Brain Institute, Gainesville, FL 32610, USA. ethan241@ufl.edu
authors.forename: E M
authors.initials: EM
authors.lastname: Anderson
authors.forename: J K
authors.initials: JK
authors.lastname: Neubert
authors.forename: R M
authors.initials: RM
authors.lastname: Caudle
mesh_terms: D017398:Alternative Splicing / Q000187:drug effects* / Q000235:genetics; D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D003720:Densitometry; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D009294:Narcotics / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D012201:Reward; D013375:Substance Withdrawal Syndrome / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013696:Temperature; D013997:Time Factors
chemical_list: C409466:NR1 NMDA receptor; D009294:Narcotics; D016194:Receptors, N-Methyl-D-Aspartate; D009020:Morphine