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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: 8.68). 01/2010; 35(1):348-9. DOI: 10.1038/npp.2009.132
Source: PubMed
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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; · 8.68 Impact Factor
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    CNS Neuroscience & Therapeutics 04/2011; 17(2):81-2. · 4.46 Impact Factor

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