title: Dopamine cross-sensitization between psychostimulant drugs and stress in healthy male volunteers.
abstract: Dysregulation of the stress response system is a potential etiological factor in the development of and relapse to multiple neuropsychiatric disorders. Previously we reported that repeated intermittent d-amphetamine administration can lead to progressively greater dopamine release, thereby providing evidence of drug-induced neurochemical sensitization. Here, we test the hypothesis that repeated exposure to d-amphetamine increases dopaminergic responses to stress; that is, produces cross-sensitization. Using positron emission tomography, we measured in 17 healthy male volunteers (mean ± s.d. = 22.1 ± 3.4 years) [(11)C]raclopride binding responses to a validated psychosocial stress task before and 2 weeks after a regimen of repeated d-amphetamine (3 × 0.3 mg kg(-1), by mouth; n = 8) or placebo (3 × lactose, by mouth; n = 9). Mood and physiological measurements were recorded throughout each session. Before the d-amphetamine regimen, exposure to the stress task increased behavioral and physiological indices of stress (anxiety, heart rate, cortisol, all P ⩽ 0.05). Following the d-amphetamine regimen, the stress-induced cortisol responses were augmented (P < 0.04), and voxel-based analyses showed larger stress-induced decreases in [(11)C]raclopride non-displaceable binding potential across the striatum. In the placebo group, re-exposure to stress led to smaller clusters of decreased [(11)C]raclopride binding, primarily in the sensorimotor striatum (P < 0.05). Together, this study provides evidence for drug × stress cross-sensitization; moreover, random exposure to stimulants and/or stress cumulatively, while enhancing dopamine release in striatal areas, may contribute to a lowered set point for psychopathologies in which altered dopamine neurotransmission is invoked.
authors.affiliation: Department of Psychology, Concordia University, Montreal, QC, Canada.|CHU Sainte Justine Hospital Research Center, University of Montreal, Montreal, QC, Canada.|Department of Psychiatry, McGill University, Montreal, QC, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Booij
authors.affiliation: Department of Psychiatry, McGill University, Montreal, QC, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Welfeld
authors.affiliation: Department of Psychiatry, McGill University, Montreal, QC, Canada.|Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, QC, Canada.|McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Leyton
authors.affiliation: McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Dagher
authors.affiliation: Center for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada.
authors.forename: I
authors.initials: I
authors.lastname: Boileau
authors.affiliation: Pole de Neurosciences Cliniques, Hôpital Pellegrin, CHU Bordeaux, Bordeaux, France.
authors.forename: I
authors.initials: I
authors.lastname: Sibon
authors.affiliation: Neurobiology Research Unit, Department of Psychiatry, Institute of Neuroscience and Mental Health, University of Alberta, Edmonton, AB, Canada.
authors.forename: G B
authors.initials: GB
authors.lastname: Baker
authors.affiliation: McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Diksic
authors.affiliation: McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
authors.forename: J-P
authors.initials: JP
authors.lastname: Soucy
authors.affiliation: Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montreal, QC, Canada.
authors.forename: J C
authors.initials: JC
authors.lastname: Pruessner
authors.affiliation: Department of Psychiatry, McGill University, Montreal, QC, Canada.
authors.forename: E
authors.initials: E
authors.lastname: Cawley-Fiset
authors.affiliation: CHU Sainte Justine Hospital Research Center, University of Montreal, Montreal, QC, Canada.
authors.forename: K F
authors.initials: KF
authors.lastname: Casey
authors.affiliation: Department of Psychiatry, McGill University, Montreal, QC, Canada.|McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Benkelfat
mesh_terms: D000328:Adult; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003913:Dextroamphetamine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000378:metabolism; D018492:Dopamine Antagonists / Q000008:administration & dosage; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography; D020891:Raclopride / Q000008:administration & dosage; D012016:Reference Values; D013315:Stress, Psychological / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000697:Central Nervous System Stimulants; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D020891:Raclopride; D003913:Dextroamphetamine; D004298:Dopamine