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Dopamine D1 and D3 receptor interactions in cocaine reward and seeking in rats

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Abstract

Rationale

Animal research has demonstrated a role of dopamine D1 and D3 receptors in cocaine reward and seeking.

Purpose and methods

Here, we investigated the potential interaction of these two dopamine receptors in cue-induced reinstatement of cocaine seeking, cocaine conditioned place preference (CPP), and cocaine self-administration in rats.

Results

The co-administration of a D3 receptor antagonist, NGB 2904 and a D1 partial agonist, SKF 77434, of doses which when administered individually produced no significant effects, prior to reinstatement or CPP tests significantly reduced lever pressing and time spent in the cocaine-paired environment, suggesting synergistic effects of the combined compounds on cocaine seeking. When given to rats self-administering cocaine under a progressive ratio schedule of reinforcement doses of NGB 2904 which were ineffective alone significantly enhanced the break point-reducing effects of SKF 77434.

Conclusions

Our results indicate that the combined treatment with a D1 receptor partial agonist and D3 receptor antagonist produces robust decreases in cocaine seeking and reward. This suggests an interaction between dopamine D1 and D3 receptors in cocaine-related behaviors.

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Authors and Affiliations

  1. Neuropsychology Doctoral Program, The Graduate Center of the City University of New York, New York, NY, 10016, USA

    E. Galaj & R. Ranaldi

  2. Department of Chemistry, Hunter College, City University of New York, 695 Park Avenue, New York, NY, 10065, USA

    W. Harding

  3. Program in Chemistry, The Graduate Center of the City University of New York, New York, NY, 10016, USA

    W. Harding

  4. Program in Biochemistry, The Graduate Center of the City University of New York, New York, NY, 10016, USA

    W. Harding

  5. Department of Psychology, Queens College, City University of New York, 65-30 Kissena Blvd, Flushing, NY, 11367, USA

    R. Ranaldi

  6. Psychology Department, Queens College, 65-30 Kissena Blvd, Flushing, NY, 11367, USA

    R. Ranaldi

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  1. E. Galaj
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  2. W. Harding
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  3. R. Ranaldi
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Correspondence to R. Ranaldi.

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Galaj, E., Harding, W. & Ranaldi, R. Dopamine D1 and D3 receptor interactions in cocaine reward and seeking in rats. Psychopharmacology 233, 3881–3890 (2016). https://doi.org/10.1007/s00213-016-4420-9

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  • DOI: https://doi.org/10.1007/s00213-016-4420-9

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