Low level of brain dopamine D2 receptors in methamphetamine abusers: Association with metabolism in the orbitofrontal cortex

N. D. Volkow, L. Chang, G. J. Wang, J. S. Fowler, Y. S. Ding, M. Sedler, J. Logan, D. Franceschi, J. Gatley, Robert Hitzemann, A. Gifford, C. Wong, N. Pappas

Research output: Contribution to journalArticle

630 Citations (Scopus)

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 difference of 16% in the caudate and 10% in the putamen). D2 receptor availability was associated with metabolic rate in the orbitofrontal cortex in abusers and in comparison subjects. Conclusions: Lower levels of dopamine D2 receptor availability have been previously reported in cocaine abusers, alcoholics, and heroine abusers. This study extends this finding to methamphetamine abusers. The association between level of dopamine D2 receptors and metabolism in the orbitofrontal cortex in methamphetamine abusers, which replicates previous findings in cocaine 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.

Original languageEnglish (US)
Pages (from-to)2015-2021
Number of pages7
JournalAmerican Journal of Psychiatry
Volume158
Issue number12
DOIs
StatePublished - 2001
Externally publishedYes

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Dopamine D2 Receptors
Methamphetamine
Prefrontal Cortex
Cocaine
Brain
Drug and Narcotic Control
Pharmaceutical Preparations
Compulsive Behavior
Raclopride
Putamen
Fluorodeoxyglucose F18
Alcoholics
Positron-Emission Tomography
Dopamine
Glucose

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Low level of brain dopamine D2 receptors in methamphetamine abusers : Association with metabolism in the orbitofrontal cortex. / Volkow, N. D.; Chang, L.; Wang, G. J.; Fowler, J. S.; Ding, Y. S.; Sedler, M.; Logan, J.; Franceschi, D.; Gatley, J.; Hitzemann, Robert; Gifford, A.; Wong, C.; Pappas, N.

In: American Journal of Psychiatry, Vol. 158, No. 12, 2001, p. 2015-2021.

Research output: Contribution to journalArticle

Volkow, ND, Chang, L, Wang, GJ, Fowler, JS, Ding, YS, Sedler, M, Logan, J, Franceschi, D, Gatley, J, Hitzemann, R, Gifford, A, Wong, C & Pappas, N 2001, 'Low level of brain dopamine D2 receptors in methamphetamine abusers: Association with metabolism in the orbitofrontal cortex', American Journal of Psychiatry, vol. 158, no. 12, pp. 2015-2021. https://doi.org/10.1176/appi.ajp.158.12.2015
Volkow, N. D. ; Chang, L. ; Wang, G. J. ; Fowler, J. S. ; Ding, Y. S. ; Sedler, M. ; Logan, J. ; Franceschi, D. ; Gatley, J. ; Hitzemann, Robert ; Gifford, A. ; Wong, C. ; Pappas, N. / Low level of brain dopamine D2 receptors in methamphetamine abusers : Association with metabolism in the orbitofrontal cortex. In: American Journal of Psychiatry. 2001 ; Vol. 158, No. 12. pp. 2015-2021.
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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 difference of 16{\%} in the caudate and 10{\%} in the putamen). D2 receptor availability was associated with metabolic rate in the orbitofrontal cortex in abusers and in comparison subjects. Conclusions: Lower levels of dopamine D2 receptor availability have been previously reported in cocaine abusers, alcoholics, and heroine abusers. This study extends this finding to methamphetamine abusers. The association between level of dopamine D2 receptors and metabolism in the orbitofrontal cortex in methamphetamine abusers, which replicates previous findings in cocaine 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.",
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T1 - Low level of brain dopamine D2 receptors in methamphetamine abusers

T2 - Association with metabolism in the orbitofrontal cortex

AU - Volkow, N. D.

AU - Chang, L.

AU - Wang, G. J.

AU - Fowler, J. S.

AU - Ding, Y. S.

AU - Sedler, M.

AU - Logan, J.

AU - Franceschi, D.

AU - Gatley, J.

AU - Hitzemann, Robert

AU - Gifford, A.

AU - Wong, C.

AU - Pappas, N.

PY - 2001

Y1 - 2001

N2 - 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 difference of 16% in the caudate and 10% in the putamen). D2 receptor availability was associated with metabolic rate in the orbitofrontal cortex in abusers and in comparison subjects. Conclusions: Lower levels of dopamine D2 receptor availability have been previously reported in cocaine abusers, alcoholics, and heroine abusers. This study extends this finding to methamphetamine abusers. The association between level of dopamine D2 receptors and metabolism in the orbitofrontal cortex in methamphetamine abusers, which replicates previous findings in cocaine 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.

AB - 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 difference of 16% in the caudate and 10% in the putamen). D2 receptor availability was associated with metabolic rate in the orbitofrontal cortex in abusers and in comparison subjects. Conclusions: Lower levels of dopamine D2 receptor availability have been previously reported in cocaine abusers, alcoholics, and heroine abusers. This study extends this finding to methamphetamine abusers. The association between level of dopamine D2 receptors and metabolism in the orbitofrontal cortex in methamphetamine abusers, which replicates previous findings in cocaine 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.

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