title: The μ opioid receptor is not involved in ethanol-stimulated dopamine release in the ventral striatum of C57BL/6J mice.
abstract: BACKGROUND
  The mu opioid receptor (MOR) has previously been found to regulate ethanol-stimulated dopamine release under some, but not all, conditions. A difference in ethanol-evoked dopamine release between male and female mixed background C57BL/6J-129SvEv mice led to questions about its ubiquitous role in these effects of ethanol. Using congenic C57BL/6J MOR knockout (KO) mice and C57BL/6J mice pretreated with an irreversible MOR antagonist, we investigated the function of this receptor in ethanol-stimulated dopamine release.
  
  
  METHODS
  Microdialysis was used to monitor dopamine release and ethanol clearance in MOR -/-, +/+, and +/- . male and female mice after intraperitoneal (i.p.) injections of 1.0, 2.0, and 3.0 g/kg ethanol (or saline). We also measured the increase in dopamine release after 5 mg/kg morphine (i.p.) in male and female MOR+/+ and -/- mice. In a separate experiment, male C57BL/6J mice were pretreated with either the irreversible MOR antagonist beta funaltrexamine (BFNA) or vehicle, and dopamine levels were monitored after administration of 2 g/kg ethanol or 5 mg/kg morphine.
  
  
  RESULTS
  Although ethanol-stimulated dopamine release at all the 3 doses of alcohol tested, there were no differences between MOR+/+, -/-, and +/- mice in these effects. Female mice had a more prolonged effect compared to males at the 1 g/kg dose. Administration of 2 g/kg ethanol also caused a similar increase in dopamine levels in both saline-pretreated and BFNA-pretreated mice. Five mg/kg morphine caused a significant increase in dopamine levels in MOR+/+ mice but not in MOR-/- mice and in saline-pretreated mice but not in BFNA-pretreated mice. Intraperitoneal saline injections had a significant, albeit small and transient, effect on dopamine release when given in a volume equivalent to the ethanol doses, but not in a volume equivalent to the 5 mg/kg morphine dose. Ethanol pharmacokinetics were similar in all genotypes and both sexes at each dose and in both pretreatment groups.
  
  
  CONCLUSIONS
  MOR is not involved in ethanol-stimulated dopamine release in the ventral striatum of C57BL/6J mice.
authors.affiliation: The University of Texas at Austin, PHAR-Pharmacology, USA.
authors.forename: Vorani
authors.initials: V
authors.lastname: Ramachandra
authors.forename: Francis
authors.initials: F
authors.lastname: Kang
authors.forename: Christine
authors.initials: C
authors.lastname: Kim
authors.forename: Alan S
authors.initials: AS
authors.lastname: Nova
authors.forename: Ankur
authors.initials: A
authors.lastname: Bajaj
authors.forename: F Scott
authors.initials: FS
authors.lastname: Hall
authors.forename: George R
authors.initials: GR
authors.lastname: Uhl
authors.forename: Rueben A
authors.initials: RA
authors.lastname: Gonzales
mesh_terms: D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017450:Receptors, Opioid, mu / Q000502:physiology*
chemical_list: D017450:Receptors, Opioid, mu; D000431:Ethanol; D004298:Dopamine