1 Institute of Mental Health Research, affiliated with the University of Ottawa, Ottawa, ON, Canada.
2 Department of Cellular & Molecular Medicine, University of Ottawa, Ottawa, ON, Canada.
3 Department of Psychiatry, McGill University, Montreal, QC, Canada.
4 Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
5 School of Psychoeducation, Université de Montréal, Montreal, QC, Canada.
6 CHU Ste-Justine Research Center, Montreal, QC, Canada.
7 Department of Psychology, Université Laval, Montreal, QC, Canada.
8 Department of Psychology, McGill University, Montreal, QC, Canada.
9 Department of Social & Preventative Medicine, Université de Montréal, Montreal, QC, Canada.
10 Department of Pediatrics & Psychology, Université de Montréal, Montreal, QC, Canada.
11 Department of Psychiatry, Université de Montréal, Montreal, QC, Canada.
12 Department of Psychiatry, McGill University, Montreal, QC, Canada. marco.leyton@mcgill.ca.
13 Montreal Neurological Institute, McGill University, Montreal, QC, Canada. marco.leyton@mcgill.ca.
14 CHU Ste-Justine Research Center, Montreal, QC, Canada. marco.leyton@mcgill.ca.
15 Department of Psychology, McGill University, Montreal, QC, Canada. marco.leyton@mcgill.ca.
16 Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, QC, Canada. marco.leyton@mcgill.ca.

Extra-striatal D2/3 receptor availability in youth at risk for addiction.

Neuropsychopharmacology. 2020 Apr 07;:

Authors: Jaworska N, Cox SML, Tippler M, Castellanos-Ryan N, Benkelfat C, Parent S, Dagher A, Vitaro F, Boivin M, Pihl RO, Côté SM, Tremblay RE, Séguin JR, Leyton M

Abstract

The neurobiological traits that confer risk for addictions remain poorly understood. However, dopaminergic function throughout the prefrontal cortex, limbic system, and upper brainstem has been implicated in behavioral features that influence addiction vulnerability, including poor impulse control and altered sensitivity to rewards and punishments (i.e., externalizing features). To test these associations in humans, we measured type-2/3 dopamine receptor (DA2/3R) availability in youth at high vs. low risk for substance use disorders (SUDs). In this study, N?=?58 youth (18.5?±?0.6?years) were recruited from cohorts that have been followed since birth. Participants with either high (high EXT; N?=?27; 16?F/11?M) or low pre-existing externalizing traits (low EXT; N?=?31; 20?F/11?M) underwent a 90-min positron emission tomography [18F]fallypride scan, and completed the Barratt impulsiveness scale (BIS-11), substance use risk profile scale (SURPS), and sensitivity to punishment and sensitivity to reward (SR) questionnaire. We found that high vs. low EXT trait participants reported elevated substance use, BIS-11, SR, and SURPS impulsivity scores, had a greater prevalence of psychiatric disorders, and exhibited higher [18F]fallypride binding potential (BPND) values in prefrontal, limbic and paralimbic regions, even when controlling for substance use. Group differences were not evident in midbrain dopamine cell body regions, but, across all participants, low midbrain BPND values were associated with low SP scores. Together, the results suggest that altered DA2/3R availability in terminal extra-striatal and dopamine cell body regions might constitute biological vulnerability traits, generating an EXT trajectory for addictions with and without co-occurring alterations in punishment sensitivity (i.e., an internalizing feature).

PMID: 32259831 [PubMed - as supplied by publisher]