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Research ArticleBehavioral Pharmacology

Different Contributions of Dopamine D1 and D2 Receptor Activity to Alcohol Potentiation of Brain Stimulation Reward in C57BL/6J and DBA/2J Mice

Eric W. Fish, Jeffrey F. DiBerto, Michael C. Krouse, J. Elliott Robinson and C. J. Malanga
Journal of Pharmacology and Experimental Therapeutics August 2014, 350 (2) 322-329; DOI: https://doi.org/10.1124/jpet.114.216135
Eric W. Fish
Bowles Center for Alcohol Studies (E.W.F., J.E.R., C.J.M.), Department of Neurology, University of North Carolina School of Medicine (J.F.D., M.C.K., J.E.R., C.J.M.), and Neurobiology Curriculum, University of North Carolina School of Medicine (J.E.R., C.J.M.), University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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Jeffrey F. DiBerto
Bowles Center for Alcohol Studies (E.W.F., J.E.R., C.J.M.), Department of Neurology, University of North Carolina School of Medicine (J.F.D., M.C.K., J.E.R., C.J.M.), and Neurobiology Curriculum, University of North Carolina School of Medicine (J.E.R., C.J.M.), University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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Michael C. Krouse
Bowles Center for Alcohol Studies (E.W.F., J.E.R., C.J.M.), Department of Neurology, University of North Carolina School of Medicine (J.F.D., M.C.K., J.E.R., C.J.M.), and Neurobiology Curriculum, University of North Carolina School of Medicine (J.E.R., C.J.M.), University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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J. Elliott Robinson
Bowles Center for Alcohol Studies (E.W.F., J.E.R., C.J.M.), Department of Neurology, University of North Carolina School of Medicine (J.F.D., M.C.K., J.E.R., C.J.M.), and Neurobiology Curriculum, University of North Carolina School of Medicine (J.E.R., C.J.M.), University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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C. J. Malanga
Bowles Center for Alcohol Studies (E.W.F., J.E.R., C.J.M.), Department of Neurology, University of North Carolina School of Medicine (J.F.D., M.C.K., J.E.R., C.J.M.), and Neurobiology Curriculum, University of North Carolina School of Medicine (J.E.R., C.J.M.), University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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Abstract

C57BL/6J (C57) and DBA/2J (DBA) mice respond differently to drugs that affect dopamine systems, including alcohol. The current study compared effects of D1 and D2 receptor agonists and antagonists, and the interaction between D1/D2 antagonists and alcohol, on intracranial self-stimulation in male C57 and DBA mice to determine the role of dopamine receptors in the effects of alcohol on brain stimulation reward (BSR). In the initial strain comparison, dose effects on BSR thresholds and maximum operant response rates were determined for the D1 receptor agonist SKF-82958 (±-6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine; 0.1–0.56 mg/kg) and antagonist SCH 23390 (+-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepinehydrochloride; 0.003–0.056 mg/kg), and the D2 receptor agonist quinpirole (0.1–3.0 mg/kg) and antagonist raclopride (0.01–0.56 mg/kg). For the alcohol interaction, SCH 23390 (0.003 mg/kg) or raclopride (0.03 mg/kg) was given before alcohol (0.6–2.4 g/kg p.o.). D1 antagonism dose-dependently elevated and SKF-82958 dose-dependently lowered BSR threshold in both strains; DBA mice were more sensitive to SKF-82958 effects. D2 antagonism dose-dependently elevated BSR threshold only in C57 mice. Low doses of quinpirole elevated BSR threshold equally in both strains, whereas higher doses of quinpirole lowered BSR threshold only in C57 mice. SCH 23390, but not raclopride, prevented lowering of BSR threshold by alcohol in DBA mice. Conversely, raclopride, but not SCH 23390, prevented alcohol potentiation of BSR in C57 mice. These results extend C57 and DBA strain differences to D1/D2 sensitivity of BSR, and suggest differential involvement of D1 and D2 receptors in the acute rewarding effects of alcohol in these two mouse strains.

Footnotes

    • Received May 1, 2014.
    • Accepted June 6, 2014.
  • This research was supported by grants from the National Institutes of Health National Institute on Alcohol Abuse and Alcoholism [Grants R01-AA018335 to C.J.M., F30-AA021312 to J.E.R., and P60-AA007573 to the UNC Bowles Center for Alcohol Studies].

  • dx.doi.org/10.1124/jpet.114.216135.

  • Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 350 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 350, Issue 2
1 Aug 2014
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Research ArticleBehavioral Pharmacology

Dopamine and Alcohol in C57 and DBA Mice

Eric W. Fish, Jeffrey F. DiBerto, Michael C. Krouse, J. Elliott Robinson and C. J. Malanga
Journal of Pharmacology and Experimental Therapeutics August 1, 2014, 350 (2) 322-329; DOI: https://doi.org/10.1124/jpet.114.216135

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Research ArticleBehavioral Pharmacology

Dopamine and Alcohol in C57 and DBA Mice

Eric W. Fish, Jeffrey F. DiBerto, Michael C. Krouse, J. Elliott Robinson and C. J. Malanga
Journal of Pharmacology and Experimental Therapeutics August 1, 2014, 350 (2) 322-329; DOI: https://doi.org/10.1124/jpet.114.216135
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