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Comparison of dopamine D1 and D5 receptor knockout mice for cocaine locomotor sensitization

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Abstract

Rationale

There is compelling support for the contribution of dopamine and the D1R-like (D1R, D5R) receptor subfamily to the behavioral and neural effects of psychostimulant drugs of abuse. The relative roles of D1R and D5R subtypes in mediating these effects are not clear.

Objectives

The objectives of this study are to directly compare (C57BL/6J congenic) D1R knockout (KO) and D5R KO mice for baseline locomotor exploration, acute locomotor responses to cocaine, and locomotor sensitization to repeated cocaine administration, and to examine cocaine conditioned place preference (CPP) in D5R KO.

Materials and methods

D1R KO, D5R KO, and wild-type (WT) were assessed for baseline open field exploration, locomotor-stimulating effects of 15 mg/kg acute cocaine and sensitized locomotor responses to cocaine after repeated home cage treatment with 20 or 30 mg/kg cocaine. D5R KO and WT were tested for CPP to 15 mg/kg cocaine.

Results

D1R KO showed modest basal hyperactivity and increased center exploration relative to WT. Acute locomotor responses to cocaine were consistently absent in D1R KO, but intact in D5R KO. D5R KO showed normal locomotor sensitization to cocaine and normal cocaine CPP. D1R KO failed to show a sensitized locomotor response to 30 mg/kg cocaine. Failure to sensitize in D1R KO was not because of excessive stereotypies. Surprisingly, D1R KO showed a strong trend for sensitization to 20 mg/kg cocaine.

Conclusions

D5R KO does not alter acute or sensitized locomotor responses to cocaine or cocaine CPP. D1R KO abolishes acute locomotor response to cocaine, but does not fully prevent locomotor sensitization to cocaine at all doses.

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Acknowledgements

We are very grateful to David Cabrera for maintenance of the breeding colonies. Research supported by the Intramural Research Programs of the National Institute of Alcohol Abuse and Alcoholism and National Institute of Neurological Disease and Stroke.

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Authors and Affiliations

  1. Section on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, 5625 Fishers Lane Rm 2N09, Rockville, MD, 20852-9411, USA

    Rose-Marie Karlsson, Kathryn R. Hefner & Andrew Holmes

  2. Molecular Neuropharmacology Section, National Institute of Neurological Disease and Stroke, National Institute of Mental Health, Bethesda, MD, USA

    David R. Sibley

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  1. Rose-Marie Karlsson
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  2. Kathryn R. Hefner
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  3. David R. Sibley
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  4. Andrew Holmes
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Correspondence to Andrew Holmes.

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Karlsson, RM., Hefner, K.R., Sibley, D.R. et al. Comparison of dopamine D1 and D5 receptor knockout mice for cocaine locomotor sensitization. Psychopharmacology 200, 117–127 (2008). https://doi.org/10.1007/s00213-008-1165-0

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  • DOI: https://doi.org/10.1007/s00213-008-1165-0

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