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Titolo:
Imaging studies on the role of dopamine in cocaine reinforcement and addiction in humans
Autore:
Volkow, ND; Fowler, JS; Wang, GJ;
Indirizzi:
Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA Brookhaven Natl Lab Upton NY USA 11973 Lab, Dept Med, Upton, NY 11973 USA Brookhaven Natl Lab, Dept Chem, Upton, NY 11973 USA Brookhaven Natl Lab Upton NY USA 11973 ab, Dept Chem, Upton, NY 11973 USA
Titolo Testata:
JOURNAL OF PSYCHOPHARMACOLOGY
fascicolo: 4, volume: 13, anno: 1999,
pagine: 337 - 345
SICI:
0269-8811(199912)13:4<337:ISOTRO>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
POSITRON EMISSION TOMOGRAPHY; DEFICIT HYPERACTIVITY DISORDER; BRAIN GLUCOSE-METABOLISM; IN-VIVO MICRODIALYSIS; THREO-METHYLPHENIDATE; NONHUMAN-PRIMATES; INTRAVENOUS METHYLPHENIDATE; TRANSPORTER OCCUPANCY; ENDOGENOUS DOPAMINE; SYNAPTIC DOPAMINE;
Keywords:
attention-deficit disorder; cingulate gyrus; dopamine D-2 receptors; dopamine transporters; fluorodeoxyglucose; methylphenidate; orbitofrontal cortex; PET; rate dependency; ritalin;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
62
Recensione:
Indirizzi per estratti:
Indirizzo: Volkow, ND Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA Brookhaven Natl Lab Upton NY USA 11973 ed, Upton, NY 11973 USA
Citazione:
N.D. Volkow et al., "Imaging studies on the role of dopamine in cocaine reinforcement and addiction in humans", J PSYCHOPH, 13(4), 1999, pp. 337-345

Abstract

We summarize our studies with positron emission tomography investigating the role of dopamine (DA) in the reinforcing effects of cocaine and methylphenidate in humans and its involvement in cocaine addiction. These studies have shown that the rate at which cocaine and methylphenidate enter the brain and block the dopamine transporters (DAT) is the variable associated withthe 'high', rather than the presence per se of the drug in the brain. Our studies also show that, while the level of DAT blockade is important in predicting the intensity of the 'high' induced by these drugs (DAT blockade >50% is required for these drugs to induce a 'high'), the rate at which DAT are blocked determines whether the 'high' is perceived or not. Thus, oral methylphenidate, which leads to slow DAT blockade, does not induce a 'high: even at doses which block DAT more than 60%. In cocaine abusers, we have shown significant reductions in DA D-2 receptors that are associated with decreased metabolism in cingulate gyrus and in orbitofrontal cortex. We suggestthat this is one of the mechanisms by which DA disruption leads to compulsive drug administration in cocaine addiction. Cocaine abusers also show significant decreases in DA release, which coupled with the reduction in D-2 receptors may result in decreased activation of reward circuits by physiological reinforcers and may perpetuate cocaine use as a means to compensate for this deficit. Thus, strategies to enhance DA brain function in ways that mimic physiological DA activity may be of help in overcoming cocaine addiction.

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Documento generato il 22/01/20 alle ore 06:39:34