title: Exposure to morphine-associated cues increases mu opioid receptor mRNA expression in the nucleus accumbens of Wistar Kyoto rats.
abstract: The Wistar-Kyoto (WKY) rat has been proposed as a model of anxiety vulnerability as it exhibits pronounced behavioral inhibition, passive avoidance, exaggerated startle response, enhanced HPA-axis activation, and active avoidance that is resistant to extinction. Accumulating evidence suggests that WKY rats respond differently to rewarding stimuli when compared to outbred strains of rat. Conditioned responding to drug-associated cues is linked with alterations in the activation of mu opioid receptors (MOR) and kappa opioid receptors (KOR) in the nucleus accumbens (NAc). Furthermore, alterations in KOR expression/activation in the NAc of WKY rats are implicated in the regulation of some of the components that make up the unique behavioral phenotype of this strain. The purpose of this study was to extend upon previous work from our laboratory by investigating conditioned morphine reward in adult male WKY and SD rats, and to examine levels of KOR mRNA and MOR mRNA in the NAc at baseline and after acquisition of morphine CPP. Our results demonstrate that SD rats displayed morphine-induced CPP to each of the six doses of morphine tested (0.5, 1.25, 2.5, 5, 7.5, or 10mg/kg). Interestingly, WKY rats demonstrated CPP for only the 1.25, 2.5, and 5mg/kg doses, yet no preference at the lowest (0.5mg/kg) or highest (7.5 and 10mg/kg) doses. qPCR analysis of MOR and KOR in the NAc revealed no strain differences in basal levels of MOR, but higher levels of KOR in WKY rats compared to those of SD rats. Interestingly, after completion of the CPP task, WKY rats had overall higher levels of NAc MOR mRNA compared to SD rats; the initial basal differences in NAc KOR levels persisted without change due to CPP in either strain. These results demonstrate that the WKY rat exhibits a unique pattern of behavioral responding to morphine and implicates differences in NAc KOR signaling as a potential source of aversion to higher doses of morphine. Additionally, the CPP-induced upregulation of NAc MOR mRNA in WKY rats warrants further investigation in terms of its potential role as a factor constituting a unique vulnerability to subsequent drug exposure.
authors.affiliation: Department of Psychology, The University of Texas at Arlington, Arlington TX, USA.
authors.forename: Torry S
authors.initials: TS
authors.lastname: Dennis
authors.affiliation: Neurobehavioral Research Lab (129), Veterans Affairs New Jersey Health Care System, East Orange, NJ, USA; Stress & Motivated Behavior Institute, Department of Neurology & Neurosciences, Rutgers, New Jersey Medical School-Rutgers, The State University of New Jersey, Newark, NJ, USA.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Beck
authors.affiliation: Neurobehavioral Research Lab (129), Veterans Affairs New Jersey Health Care System, East Orange, NJ, USA; Stress & Motivated Behavior Institute, Department of Neurology & Neurosciences, Rutgers, New Jersey Medical School-Rutgers, The State University of New Jersey, Newark, NJ, USA.
authors.forename: Tara P
authors.initials: TP
authors.lastname: Cominski
authors.affiliation: Department of Psychology, The University of Texas at Arlington, Arlington TX, USA.
authors.forename: Samara A M
authors.initials: SAM
authors.lastname: Bobzean
authors.affiliation: Department of Pharmacology & Physiology, Rutgers, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA.
authors.forename: Eldo V
authors.initials: EV
authors.lastname: Kuzhikandathil
authors.affiliation: Neurobehavioral Research Lab (129), Veterans Affairs New Jersey Health Care System, East Orange, NJ, USA; Stress & Motivated Behavior Institute, Department of Neurology & Neurosciences, Rutgers, New Jersey Medical School-Rutgers, The State University of New Jersey, Newark, NJ, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Servatius
authors.affiliation: Department of Psychology, The University of Texas at Arlington, Arlington TX, USA. Electronic address: Perrotti@uta.edu.
authors.forename: Linda I
authors.initials: LI
authors.lastname: Perrotti
mesh_terms: D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D003463:Cues; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D011921:Rats, Inbred WKY; D017473:Receptors, Opioid, kappa / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D009020:Morphine
keywords: Anxiety; Avoidance; Conditioned place preference; Male; Reward