Abstract
Tobacco smoking is a significant cause of preventable morbidity and mortality globally. Current pharmacological approaches to treat tobacco use disorder (TUD) are only partly effective and novel approaches are needed. Dopamine has a well-established role in substance use disorders, including TUD, and there has been a long-standing interest in developing agents that target the dopaminergic system to treat substance use disorders. Dopamine has 5 receptor subtypes (DRD1 to DRD5). Given the localization and safety profile of the dopamine receptor D3 (DRD3), it is of therapeutic potential for TUD. In this chapter, the preclinical and clinical literature investigating the role of DRD3 in processes relevant to TUD will be reviewed, including in nicotine reinforcement, drug reinstatement, conditioned stimuli and cue-reactivity, executive function, and withdrawal. Similarities and differences in findings from the animal and human work will be synthesized and findings will be discussed in relation to the therapeutic potential of targeting DRD3 in TUD.
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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), Alkermes, and Universal Ibogaine. Lastly, Dr. Le Foll has received in-kind donations of nabiximols from GW Pharmaceuticals for the 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 a consultant for Shinogi. He is supported by CAMH, Waypoint Centre for Mental Health Care, 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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Butler, K., Le Foll, B., Di Ciano, P. (2022). The Role of Dopamine D3 Receptors in Tobacco Use Disorder: A Synthesis of the Preclinical and Clinical Literature. 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_392
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