The Mu Opioid Receptor Is Not Involved in Ethanol-Stimulated Dopamine Release in the Ventral Striatum of C57BL/6J Mice

Authors

  • Vorani Ramachandra,

    1. From The University of Texas at Austin (VR, FK, CK, ASN, AB, RAG), PHAR-Pharmacology, Austin, Texas; Molecular Biology Branch (FSH, GRU), National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, Maryland.
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  • Francis Kang,

    1. From The University of Texas at Austin (VR, FK, CK, ASN, AB, RAG), PHAR-Pharmacology, Austin, Texas; Molecular Biology Branch (FSH, GRU), National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, Maryland.
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  • Christine Kim,

    1. From The University of Texas at Austin (VR, FK, CK, ASN, AB, RAG), PHAR-Pharmacology, Austin, Texas; Molecular Biology Branch (FSH, GRU), National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, Maryland.
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  • Alan S. Nova,

    1. From The University of Texas at Austin (VR, FK, CK, ASN, AB, RAG), PHAR-Pharmacology, Austin, Texas; Molecular Biology Branch (FSH, GRU), National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, Maryland.
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  • Ankur Bajaj,

    1. From The University of Texas at Austin (VR, FK, CK, ASN, AB, RAG), PHAR-Pharmacology, Austin, Texas; Molecular Biology Branch (FSH, GRU), National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, Maryland.
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  • F. Scott Hall,

    1. From The University of Texas at Austin (VR, FK, CK, ASN, AB, RAG), PHAR-Pharmacology, Austin, Texas; Molecular Biology Branch (FSH, GRU), National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, Maryland.
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  • George R. Uhl,

    1. From The University of Texas at Austin (VR, FK, CK, ASN, AB, RAG), PHAR-Pharmacology, Austin, Texas; Molecular Biology Branch (FSH, GRU), National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, Maryland.
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  • Rueben A. Gonzales

    1. From The University of Texas at Austin (VR, FK, CK, ASN, AB, RAG), PHAR-Pharmacology, Austin, Texas; Molecular Biology Branch (FSH, GRU), National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, Maryland.
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Reprint requests: Rueben A. Gonzales, The University of Texas at Austin, PHAR-Pharmacology, 1 University Station A1915, Austin, TX 78712; Tel.: 512 471 5192; Fax: 512 475 6088; E-mail: rgonzales@mail.utexas.edu

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.

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