Journal ArticleDOI
Low Level of Brain Dopamine D2 Receptors in Methamphetamine Abusers: Association With Metabolism in the Orbitofrontal Cortex
Nora D. Volkow,Linda Chang,Gene-Jack Wang,Joanna S. Fowler,Y.-S. Ding,Mark J. Sedler,Jean Logan,Dinko Franceschi,John Gatley,Robert Hitzemann,Andrew N. Gifford,Christopher Wong,Naomi Pappas +12 more
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TLDR
The association between level of dopamine D2 receptors and metabolism in the orbit ofrontal cortex in methamphetamine abusers suggests that D2 receptor-mediated dysregulation of the orbitofrontal cortex could underlie a common mechanism for loss of control and compulsive drug intake in drug-addicted subjects.Abstract:
OBJECTIVE: The role of dopamine in the addictive process (loss of control and compulsive drug intake) is poorly understood. A consistent finding in drug-addicted subjects is a lower level of dopamine D2 receptors. In cocaine abusers, low levels of D2 receptors are associated with a lower level of metabolism in the orbitofrontal cortex. Because the orbitofrontal cortex is associated with compulsive behaviors, its disruption may contribute to compulsive drug intake in addicted subjects. This study explored whether a similar association occurs in methamphetamine abusers. METHOD: Fifteen methamphetamine abusers and 20 non-drug-abusing comparison subjects were studied with positron emission tomography (PET) and [11C]raclopride to assess the availability of dopamine D2 receptors and with [18F]fluorodeoxyglucose to assess regional brain glucose metabolism, a marker of brain function. RESULTS: Methamphetamine abusers had a significantly lower level of D2 receptor availability than comparison subjects (a differenc...read more
Citations
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Journal ArticleDOI
Neurocircuitry of Addiction
George F. Koob,Nora D. Volkow +1 more
TL;DR: The delineation of the neurocircuitry of the evolving stages of the addiction syndrome forms a heuristic basis for the search for the molecular, genetic, and neuropharmacological neuroadaptations that are key to vulnerability for developing and maintaining addiction.
Journal ArticleDOI
Drug Addiction and Its Underlying Neurobiological Basis: Neuroimaging Evidence for the Involvement of the Frontal Cortex
Rita Z. Goldstein,Nora D. Volkow +1 more
TL;DR: An integrated model of drug addiction that encompasses intoxication, bingeing, withdrawal, and craving is proposed, and results imply that addiction connotes cortically regulated cognitive and emotional processes, which result in the overvaluing of drug reinforcers, the undervalued of alternative rein forcers, and deficits in inhibitory control for drug responses.
Journal ArticleDOI
Dysfunction of the prefrontal cortex in addiction: neuroimaging findings and clinical implications
TL;DR: Functional neuroimaging studies conducted in the past decade that have expanded the understanding of the involvement of the PFC in drug addiction are focused on.
Journal ArticleDOI
Neurobiology of addiction: A neurocircuitry analysis.
George F. Koob,Nora D. Volkow +1 more
TL;DR: Molecular genetic studies have identified transduction and transcription factors that act in neurocircuitry associated with the development and maintenance of addiction that might mediate initial vulnerability, maintenance, and relapse associated with addiction.
Journal ArticleDOI
Impulsivity, compulsivity, and top-down cognitive control.
TL;DR: The results indicate that the vulnerability to stimulant addiction may depend on an impulsivity endophenotype, and characterize in neurobehavioral and neurochemical terms a rodent model of impulsivity based on premature responding in an attentional task.
References
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Journal ArticleDOI
Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter
TL;DR: In homozygote mice, dopamine persists at least 100 times longer in the extracellular space, explaining the biochemical basis of the hyperdopaminergic phenotype and demonstrating the critical role of the transporter in regulating neurotransmission.
Journal ArticleDOI
Cellular and molecular mechanisms of drug dependence.
George F. Koob,Floyd E. Bloom +1 more
TL;DR: The molecular and cellular actions of three classes of abused drugs--opiates, psychostimulants, and ethanol--are reviewed in the context of behavioral studies of drug dependence.
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Brain dopamine and obesity.
Gene-Jack Wang,Gene-Jack Wang,Nora D. Volkow,Nora D. Volkow,Jean Logan,Naoml R Pappas,Christopher Wong,Wel Zhu,Noelwah Netusll,Joanna S. Fowler +9 more
TL;DR: Dopamine modulates motivation and reward circuits and hence dopamine deficiency in obese individuals may perpetuate pathological eating as a means to compensate for decreased activation of these circuits.
Journal ArticleDOI
Relative reward preference in primate orbitofrontal cortex
TL;DR: Neurons in the orbitofrontal cortex of monkeys process the motivational value of rewarding outcomes of voluntary action, mainly irrespective of the spatial and visual features of reward-predicting stimuli and behavioural reactions.
Journal ArticleDOI
Addiction, a Disease of Compulsion and Drive: Involvement of the Orbitofrontal Cortex
Nora D. Volkow,Joanna S. Fowler +1 more
TL;DR: It is implied that pleasure per se is not enough to maintain compulsive drug administration in the drugaddicted subject and that drugs that could interfere with the activation of the striato-thalamo-orbitofrontal circuit could be beneficial in the treatment of drug addiction.