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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    Full-text · Article · Apr 2011 · CNS Neuroscience & Therapeutics
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    ABSTRACT: Schizophrenia has long been associated with an imbalance in dopamine (DA) neurotransmission, and brain imaging has played an important role in advancing our knowledge and providing evidence for the dopaminergic abnormalities. This chapter reviews the evidence for DA dysfunction in different brain regions in schizophrenia, in particular striatal, extrastriatal, and prefrontal regions, with emphasis on recently published findings. As opposed to the traditional view that most striatal dopaminergic excess, associated with the positive symptoms of schizophrenia, involves the dopaminergic mesolimbic pathway, recent evidence points to the nigrostriatal pathway as the area of highest dysregulation. Furthermore, evidence from translational research suggests that dopaminergic excess may be present in the prodromal phase, and may by itself, as suggested by the phenotype observed in transgenic mice with developmental overexpression of dorso-striatal D(2) receptors, be an early pathogenic condition, leading to irreversible cortical dysfunction.
    No preview · Article · Nov 2012 · Handbook of experimental pharmacology
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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.
    No preview · Article · Dec 2013 · Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology
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