Advances in PET analyses of stress and dopamine

CAMH, PET centre, Toronto, ON, Canada.
Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology (Impact Factor: 7.05). 01/2010; 35(1):348-9. DOI: 10.1038/npp.2009.132
Source: PubMed


Neuropsychopharmacology, the official publication of the American College of Neuropsychopharmacology, publishing the highest quality original research and advancing our understanding of the brain and behavior.

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    CNS Neuroscience & Therapeutics 04/2011; 17(2):81-2. DOI:10.1111/j.1755-5949.2011.00250.x · 3.93 Impact Factor
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    ABSTRACT: Research on the environmental risk factors for schizophrenia has focused on either psychosocial stress or drug exposure, with limited investigation of their interaction. A heightened dopaminergic stress response in patients with schizophrenia and individuals at clinical high risk (CHR) supports the dopaminergic sensitization hypothesis. Cannabis is believed to contribute to the development of schizophrenia, possibly through a cross-sensitization with stress. Twelve CHR and 12 cannabis-using CHR (CHR-CU, 11 dependent) subjects underwent [(11)C]-(+)-PHNO positron emission tomography scans while performing a sensorimotor control task (SMCT) and a stress condition (Montreal Imaging Stress task; MIST). The simplified reference tissue model was used to obtain binding potential relative to non-displaceable binding (BPND) in the whole striatum, its functional subdivisions (limbic striatum (LST), associative striatum (AST) and sensorimotor striatum (SMST)), globus pallidus (GP) and substantia nigra (SN). Changes in BPND, reflecting alterations in synaptic dopamine levels, were tested with ANOVA. SMCT BPND was not significantly different between groups in any brain region (P>0.21). While stress elicited a significant reduction in BPND in the CHR group, CHR-CU group exhibited an increase in BPND. Stress-induced changes in regional BPND between CHR-CU and CHR were significantly different in AST (P<0.001), LST (P=0.007), SMST (P=0.002), SN (P=0.021) and whole striatum (P=0.001), with trend level in the GP (P=0.099). All subjects experienced an increase in positive (attenuated) psychotic symptoms (P=0.001) following the stress task. Our results suggest altered DA stress reactivity in CHR who concurrently use cannabis, as compared to CHR. Our finding does not support the cross-sensitization hypothesis, which posits greater dopaminergic reactivity to stress in CHR cannabis users, but adds to the growing body of literature showing reduced dopamine (stress) response in addiction.Neuropsychopharmacology accepted article preview online, 24 December 2013. doi:10.1038/npp.2013.347.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 12/2013; 39(6). DOI:10.1038/npp.2013.347 · 7.05 Impact Factor
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    ABSTRACT: Adolescence is characterized by heightened risk-taking, including substance misuse. These behavioral patterns are influenced by ontogenic changes in neurotransmitter systems, particularly the dopamine system, which is fundamentally involved in the neural coding of reward and motivated approach behavior. During adolescence, this system evidences a peak in activity. At the same time, the dopamine (DA) system is neuroplastically altered by substance abuse, impacting subsequent function. Here, we describe properties of the dopamine system that change with typical adolescent development and that are altered with substance abuse. Much of this work has been gleaned from animal models due to limitations in measuring dopamine in pediatric samples. Structural and functional neuroimaging techniques have been used to examine structures that are heavily DA-innervated; they measure morphological and functional changes with age and with drug exposure. Presenting marijuana abuse as an exemplar, we consider recent findings that support an adolescent peak in DA-driven reward-seeking behavior and related deviations in motivational systems that are associated with marijuana abuse/dependence. Clinicians are advised that (1) chronic adolescent marijuana use may lead to deficiencies in incentive motivation, (2) that this state is due to marijuana's interactions with the developing DA system, and (3) that treatment strategies should be directed to remediating resultant deficiencies in goal-directed activity.
    CNS spectrums 06/2015; 20(4):1-15. DOI:10.1017/S1092852915000395 · 2.71 Impact Factor

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