title: δ-opioid receptor function in the dorsal striatum plays a role in high levels of ethanol consumption in rats.
abstract: Binge-like patterns of excessive drinking during young adulthood increase the propensity for alcohol use disorders (AUDs) later in adult life; however, the mechanisms that drive this are not completely understood. Previous studies showed that the δ-opioid peptide receptor (DOP-R) is dynamically regulated by exposure to ethanol and that the DOP-R plays a role in ethanol-mediated behaviors. The aim of this study was to determine the role of the DOP-R in high ethanol consumption from young adulthood through to late adulthood by measuring DOP-R-mediated [(35)S]GTPγS binding in brain membranes and DOP-R-mediated analgesia using a rat model of high ethanol consumption in Long Evans rats. We show that DOP-R activity in the dorsal striatum and DOP-R-mediated analgesia changes during development, being highest during early adulthood and reduced in late adulthood. Intermittent access to ethanol but not continuous ethanol or water from young adulthood leads to an increase in DOP-R activity in the dorsal striatum and DOP-R-mediated analgesia into late adulthood. Multiple microinfusions of naltrindole into the dorsal striatum or multiple systemic administration of naltrindole reduces ethanol consumption, and following termination of treatment, DOP-R activity in the dorsal striatum is attenuated. These findings suggest that DOP-R activity in the dorsal striatum plays a role in high levels of ethanol consumption and suggest that targeting the DOP-R is an alternative strategy for the treatment of AUDs.
authors.affiliation: Ernest Gallo Clinic and Research Center, University of California, San Francisco, Emeryville, CA 94608, USA.
authors.forename: Carsten K
authors.initials: CK
authors.lastname: Nielsen
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Simms
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.forename: Douglas
authors.initials: D
authors.lastname: Mill
authors.forename: Henry
authors.initials: H
authors.lastname: Yi
authors.forename: Allison A
authors.initials: AA
authors.lastname: Feduccia
authors.forename: Nathan
authors.initials: N
authors.lastname: Santos
authors.forename: Selena E
authors.initials: SE
authors.lastname: Bartlett
mesh_terms: D000367:Age Factors; D000428:Alcohol Drinking / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D000698:Analgesia / Q000379:methods / Q000523:psychology; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D004357:Drug Synergism; D000431:Ethanol / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D008297:Male; D008845:Microinjections; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D011869:Radioligand Assay / Q000379:methods / Q000523:psychology*; D051381:Rats; D020318:Rats, Long-Evans; D017465:Receptors, Opioid, delta / Q000378:metabolism / Q000502:physiology*; D013462:Sulfur Radioisotopes
chemical_list: D011804:Quinolines; D017465:Receptors, Opioid, delta; D013462:Sulfur Radioisotopes; C094142:TAN 67; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D000431:Ethanol; D009271:Naltrexone; C055382:naltrindole