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The Mu Opioid Receptor Is Not Involved in Ethanol‐Stimulated Dopamine Release in the Ventral Striatum of C57BL/6J Mice
Author(s) -
Ramachandra Vorani,
Kang Francis,
Kim Christine,
Nova Alan S.,
Bajaj Ankur,
Scott Hall F.,
Uhl George R.,
Gonzales Rueben A.
Publication year - 2011
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2010.01423.x
Subject(s) - striatum , dopamine , opioid , ventral striatum , ethanol , chemistry , c57bl/6 , receptor , pharmacology , endocrinology , medicine , neuroscience , biology , biochemistry
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.