title: Cocaine-induced suppression of saccharin intake and morphine modulation of Ca²⁺ channel currents in sensory neurons of OPRM1 A118G mice.
abstract: Several studies have shown that human carriers of the single nucleotide polymorphism of the μ-opioid receptor, OPRM1 A118G, exhibit greater drug and alcohol use, increased sensitivity to pain, and reduced sensitivity to the antinociceptive effects of opiates. In the present study, we employed a 'humanized' mouse model containing the wild-type (118AA) or variant (118GG) allele to examine behavior in our model of drug-induced suppression of a natural reward cue and to compare the morphine pharmacological profile in acutely isolated sensory neurons. Compared with 118AA mice, our results demonstrate that homozygous 118GG mice exhibit greater avoidance of the cocaine-paired saccharin cue, a behavior linked to an aversive withdrawal-like state. Electrophysiological recordings confirmed the reduced modulation of Ca(2+) channels by morphine in trigeminal ganglion (TG) neurons from 118GG mice compared to the 118AA control cells. However, repeated cocaine exposure in 118GG mice led to a leftward shift of the morphine concentration-response relationship when compared with 118GG control mice, while a rightward shift was observed in 118AA mice. These results suggest that cocaine exposure of mice carrying the 118G allele leads to a heightened sensitivity of the reward system and a blunted modulation of Ca(2+) channels by morphine in sensory neurons.
authors.affiliation: Department of Neural and Behavioral Sciences, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA. Electronic address: csf5@psu.edu.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Freet
authors.affiliation: Department of Neural and Behavioral Sciences, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Ballard
authors.affiliation: Department of Neural and Behavioral Sciences, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
authors.forename: Danielle N
authors.initials: DN
authors.lastname: Alexander
authors.affiliation: Department of Neural and Behavioral Sciences, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
authors.forename: Taylor A
authors.initials: TA
authors.lastname: Cox
authors.affiliation: Department of Neural and Behavioral Sciences, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
authors.forename: Caesar G
authors.initials: CG
authors.lastname: Imperio
authors.affiliation: Department of Neural and Behavioral Sciences, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
authors.forename: Nnaemeka
authors.initials: N
authors.lastname: Anosike
authors.affiliation: Department of Neural and Behavioral Sciences, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
authors.forename: Alyssa B
authors.initials: AB
authors.lastname: Carter
authors.affiliation: Department of Anesthesiology, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
authors.forename: Saifeldin
authors.initials: S
authors.lastname: Mahmoud
authors.affiliation: Department of Anesthesiology, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Ruiz-Velasco
authors.affiliation: Department of Neural and Behavioral Sciences, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
authors.forename: Patricia S
authors.initials: PS
authors.lastname: Grigson
mesh_terms: D000818:Animals; D016739:Behavior, Addictive / Q000503:physiopathology; D015220:Calcium Channels / Q000378:metabolism; D002478:Cells, Cultured; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000503:physiopathology; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D008822:Mice, Transgenic; D020641:Polymorphism, Single Nucleotide; D017450:Receptors, Opioid, mu / Q000235:genetics / Q000378:metabolism*; D012201:Reward; D012439:Saccharin / Q000008:administration & dosage*; D011984:Sensory Receptor Cells / Q000187:drug effects* / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology; D012668:Trigeminal Ganglion / Q000187:drug effects / Q000502:physiology
chemical_list: D015220:Calcium Channels; D018765:Dopamine Uptake Inhibitors; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; D012439:Saccharin; D003042:Cocaine
keywords: Addiction; Natural rewards; Opiates; Pain; Reward comparison