Lack of operant ethanol self-administration in dopamine D2 receptor knockout mice

F. O. Risinger, P. A. Freeman, M. Rubinstein, M. J. Low, David Grandy

    Research output: Contribution to journalArticle

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    Abstract

    Rationale: Dopamine D2 receptors are postulated to play an important role in modulating the reinforcing effects of abused drugs including ethanol. Objectives: This experiment examined operant ethanol self-administration in dopamine D2 receptor knockout (KO) mice and wild-type (WT) mice using a continuous access procedure. Methods: Adult male KO and WT mice were trained in 30-min sessions to perform a lever press response for access to 10% v/v ethanol. After training, the mice were placed in test chambers on a continuous (23 h/day) basis with access to food (one lever press, i.e., FR1), 10% v/v ethanol (four lever presses, i.e., FR4), and water from a sipper tube (phase 1). After 30 consecutive sessions, response patterns were determined for 0, 5, 10, 20 and 30% v/v ethanol (phase 2). Saccharin (0.2% w/v) was subsequently added to the ethanol mixture and responding was examined for 0, 5, 10 and 20% ethanol (phase 3). Results: During phase 1, WT mice displayed higher ethanol-lever responding compared to KO mice. Food lever responding and water intake was the same in both genotypes. During phase 2, WT mice displayed concentration-dependent ethanol lever responding, whereas KO mice responded at low rates regardless of ethanol concentration. WT mice also responded more for food compared to KO mice. Each genotype showed similar water intakes except at the 20% ethanol concentration, where WT mice had lower intakes. During phase 3, WT mice continued to show higher responding for all concentrations including saccharin alone. WT mice also continued to respond more for food compared to KO mice, but drank less water. In each phase, WT mice displayed episodic (bout) responding on the ethanol lever. KO mice did not respond for ethanol in bouts. Conclusions: Reduced responding in the KO mice for several reinforcers including ethanol indicates a more general role for dopamine D2 receptors in motivated responding rather than a specific role in ethanol reinforcement.

    Original languageEnglish (US)
    Pages (from-to)343-350
    Number of pages8
    JournalPsychopharmacology
    Volume152
    Issue number3
    DOIs
    StatePublished - 2000

    Fingerprint

    Self Administration
    Dopamine D2 Receptors
    Knockout Mice
    Ethanol
    Saccharin
    Food
    Drinking
    Genotype
    Water

    Keywords

    • Continuous access
    • Dopamine D receptor knockout mice
    • Ethanol self-administration
    • Reinforcement

    ASJC Scopus subject areas

    • Pharmacology

    Cite this

    Risinger, F. O., Freeman, P. A., Rubinstein, M., Low, M. J., & Grandy, D. (2000). Lack of operant ethanol self-administration in dopamine D2 receptor knockout mice. Psychopharmacology, 152(3), 343-350. https://doi.org/10.1007/s002130000548

    Lack of operant ethanol self-administration in dopamine D2 receptor knockout mice. / Risinger, F. O.; Freeman, P. A.; Rubinstein, M.; Low, M. J.; Grandy, David.

    In: Psychopharmacology, Vol. 152, No. 3, 2000, p. 343-350.

    Research output: Contribution to journalArticle

    Risinger, FO, Freeman, PA, Rubinstein, M, Low, MJ & Grandy, D 2000, 'Lack of operant ethanol self-administration in dopamine D2 receptor knockout mice', Psychopharmacology, vol. 152, no. 3, pp. 343-350. https://doi.org/10.1007/s002130000548
    Risinger, F. O. ; Freeman, P. A. ; Rubinstein, M. ; Low, M. J. ; Grandy, David. / Lack of operant ethanol self-administration in dopamine D2 receptor knockout mice. In: Psychopharmacology. 2000 ; Vol. 152, No. 3. pp. 343-350.
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    abstract = "Rationale: Dopamine D2 receptors are postulated to play an important role in modulating the reinforcing effects of abused drugs including ethanol. Objectives: This experiment examined operant ethanol self-administration in dopamine D2 receptor knockout (KO) mice and wild-type (WT) mice using a continuous access procedure. Methods: Adult male KO and WT mice were trained in 30-min sessions to perform a lever press response for access to 10{\%} v/v ethanol. After training, the mice were placed in test chambers on a continuous (23 h/day) basis with access to food (one lever press, i.e., FR1), 10{\%} v/v ethanol (four lever presses, i.e., FR4), and water from a sipper tube (phase 1). After 30 consecutive sessions, response patterns were determined for 0, 5, 10, 20 and 30{\%} v/v ethanol (phase 2). Saccharin (0.2{\%} w/v) was subsequently added to the ethanol mixture and responding was examined for 0, 5, 10 and 20{\%} ethanol (phase 3). Results: During phase 1, WT mice displayed higher ethanol-lever responding compared to KO mice. Food lever responding and water intake was the same in both genotypes. During phase 2, WT mice displayed concentration-dependent ethanol lever responding, whereas KO mice responded at low rates regardless of ethanol concentration. WT mice also responded more for food compared to KO mice. Each genotype showed similar water intakes except at the 20{\%} ethanol concentration, where WT mice had lower intakes. During phase 3, WT mice continued to show higher responding for all concentrations including saccharin alone. WT mice also continued to respond more for food compared to KO mice, but drank less water. In each phase, WT mice displayed episodic (bout) responding on the ethanol lever. KO mice did not respond for ethanol in bouts. Conclusions: Reduced responding in the KO mice for several reinforcers including ethanol indicates a more general role for dopamine D2 receptors in motivated responding rather than a specific role in ethanol reinforcement.",
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    AB - Rationale: Dopamine D2 receptors are postulated to play an important role in modulating the reinforcing effects of abused drugs including ethanol. Objectives: This experiment examined operant ethanol self-administration in dopamine D2 receptor knockout (KO) mice and wild-type (WT) mice using a continuous access procedure. Methods: Adult male KO and WT mice were trained in 30-min sessions to perform a lever press response for access to 10% v/v ethanol. After training, the mice were placed in test chambers on a continuous (23 h/day) basis with access to food (one lever press, i.e., FR1), 10% v/v ethanol (four lever presses, i.e., FR4), and water from a sipper tube (phase 1). After 30 consecutive sessions, response patterns were determined for 0, 5, 10, 20 and 30% v/v ethanol (phase 2). Saccharin (0.2% w/v) was subsequently added to the ethanol mixture and responding was examined for 0, 5, 10 and 20% ethanol (phase 3). Results: During phase 1, WT mice displayed higher ethanol-lever responding compared to KO mice. Food lever responding and water intake was the same in both genotypes. During phase 2, WT mice displayed concentration-dependent ethanol lever responding, whereas KO mice responded at low rates regardless of ethanol concentration. WT mice also responded more for food compared to KO mice. Each genotype showed similar water intakes except at the 20% ethanol concentration, where WT mice had lower intakes. During phase 3, WT mice continued to show higher responding for all concentrations including saccharin alone. WT mice also continued to respond more for food compared to KO mice, but drank less water. In each phase, WT mice displayed episodic (bout) responding on the ethanol lever. KO mice did not respond for ethanol in bouts. Conclusions: Reduced responding in the KO mice for several reinforcers including ethanol indicates a more general role for dopamine D2 receptors in motivated responding rather than a specific role in ethanol reinforcement.

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