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A Historical Perspective on the Dopamine D3 Receptor

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Therapeutic Applications of Dopamine D3 Receptor Function

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 60))

Abstract

Before 1990, the multiplicity of dopamine receptors beyond D1 and D2 had remained a controversial concept, despite its substantial clinical implications, at a time when it was widely accepted that dopamine interacted with only two receptor subtypes, termed D1 and D2, differing one from the other by their pharmacological specificity and opposite effects on adenylyl cyclase. It was also generally admitted that the therapeutic efficacy of antipsychotics resulted from blockade of D2 receptors. Thanks to molecular biology techniques, the D3 receptor could be characterized as a distinct molecular entity having a restricted anatomical gene expression and different signaling, which could imply peculiar functions in controlling cognitive and emotional behaviors. Due to the structural similarities of D2 and D3 receptors, the search for D3-selective compounds proved to be difficult, but nevertheless led to the identification of fairly potent and in vitro and in vivo selective compounds. The latter permitted to confirm a role of D3 receptors in motor functions, addiction, cognition, and schizophrenia, which paved the way for the development of new drugs for the treatment of psychiatric disorders.

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Authors and Affiliations

  1. Biodol Therapeutics, Clapiers, France

    Pierre Sokoloff

  2. Translational Addiction Research Laboratory, Centre for Addiction and Mental Health, Toronto, ON, Canada

    Bernard Le Foll

  3. Campbell Family Mental Health Research Institute, CAMH, Toronto, ON, Canada

    Bernard Le Foll

  4. Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, ON, Canada

    Bernard Le Foll

  5. Departments of Family and Community Medicine, University of Toronto, Toronto, ON, Canada

    Bernard Le Foll

  6. Institute of Medical Science, University of Toronto, Toronto, ON, Canada

    Bernard Le Foll

  7. Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada

    Bernard Le Foll

  8. Waypoint Research Institute, Waypoint Centre for Mental Health Care, 5, Penetanguishene, ON, Canada

    Bernard Le Foll

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  1. Pierre Sokoloff
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Correspondence to Bernard Le Foll .

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Editors and Affiliations

  1. Addiction Imaging Research Group, Centre for Addiction and Mental Health, Toronto, ON, Canada

    Isabelle Boileau

  2. Dept of Molecular&Translational Medicine, University of Brescia, Brescia, Italy

    Ginetta Collo

Ethics declarations

Dr. Bernard Le Foll has obtained funding from Pfizer Inc. (GRAND Awards, including salary support) for investigator-initiated projects. Dr. Le Foll has obtained funding from Indivior for a clinical trial sponsored by Indivior. Dr. Le Foll has in-kind donations of cannabis products from Aurora Cannabis Enterprises Inc. and study medication donations from Pfizer Inc. (varenicline for smoking cessation) and Bioprojet Pharma. He was also provided a coil for a transcranial magnetic stimulation (TMS) study from Brainsway. Dr. Le Foll has obtained industry funding from Canopy Growth Corporation (through research grants handled by the Centre for Addiction and Mental Health and the University of Toronto), Bioprojet Pharma, Alcohol Countermeasure Systems (ACS), and Alkermes. Lastly, Dr. Le Foll has received in-kind donations of nabiximols from GW Pharmaceuticals for past studies funded by CIHR and NIH.

He has participated in a session of a National Advisory Board Meeting (Emerging Trends BUP-XR) for Indivior Canada and has been consultant for Shinogi. He is supported by CAMH, a clinician-scientist award from the department of Family and Community Medicine of the University of Toronto and a Chair in Addiction Psychiatry from the department of Psychiatry of University of Toronto.

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Sokoloff, P., Le Foll, B. (2022). A Historical Perspective on the Dopamine D3 Receptor. In: Boileau, I., Collo, G. (eds) Therapeutic Applications of Dopamine D3 Receptor Function. Current Topics in Behavioral Neurosciences, vol 60. Springer, Cham. https://doi.org/10.1007/7854_2022_315

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