Association of methylphenidate-induced craving with changes in right striato-orbitofrontal metabolism in cocaine abusers

Implications in addiction

Nora D. Volkow, Gene Jack Wang, Joanna S. Fowler, Robert Hitzemann, Burton Angrist, Samuel J. Gatley, Jean Logan, Yu Shin Ding, Naomi Pappas

Research output: Contribution to journalArticle

239 Citations (Scopus)

Abstract

Objective: The authors have shown that decreases in dopamine D2 receptors in cocaine abusers were associated with decreased metabolism in the cingulate and prefrontal and orbitofrontal cortices. To assess whether increasing dopamine would reverse these metabolic decrements, they measured the effects of methylphenidate, a drug that increases dopamine, on brain glucose metabolism in 20 cocaine abusers. Method: The subjects underwent two [18F]fluorodeoxyglucose positron emission tomography scans, one after two sequential placebo injections and one after two intravenous doses of methylphenidate. D2 receptors were measured with [11C]raclopride to evaluate their relation to methylphenidate-induced metabolic changes. Results: Methylphenidate induced variable changes in brain metabolism: subjects with the higher D2 measures tended to increase metabolism, whereas those with the lower D2 measures tended to decrease metabolism. Methylphenidate's effects were significant for increases in metabolism in the superior cingulate, right thalamus, and cerebellum. Methylphenidate-induced changes in the right orbitofrontal cortex and right striatum were associated with craving, and those in the prefrontal cortex were associated with mood. Conclusions: Although methylphenidate increased metabolism in the superior cingulate, it only increased metabolism in orbitofrontal or prefrontal cortices in the subjects in whom it enhanced craving and mood, respectively. This indicates that dopamine enhancement is not sufficient per se to increase metabolism in these frontal regions. Activation of the right orbitofrontal cortex and right striatum (brain regions found to be abnormal in compulsive disorders) in the subjects reporting craving may be one of the mechanisms underlying compulsive drug administration in addicted persons. The predominant correlation of craving with right but not left brain regions suggests laterality of reinforcing and/or conditioned responses.

Original languageEnglish (US)
Pages (from-to)19-26
Number of pages8
JournalAmerican Journal of Psychiatry
Volume156
Issue number1
StatePublished - Jan 1999
Externally publishedYes

Fingerprint

Methylphenidate
Cocaine
Prefrontal Cortex
Brain
Dopamine
Raclopride
Craving
Dopamine Agents
Dopamine D2 Receptors
Gyrus Cinguli
Fluorodeoxyglucose F18
Thalamus
Positron-Emission Tomography
Cerebellum
Placebos
Glucose
Injections

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Association of methylphenidate-induced craving with changes in right striato-orbitofrontal metabolism in cocaine abusers : Implications in addiction. / Volkow, Nora D.; Wang, Gene Jack; Fowler, Joanna S.; Hitzemann, Robert; Angrist, Burton; Gatley, Samuel J.; Logan, Jean; Ding, Yu Shin; Pappas, Naomi.

In: American Journal of Psychiatry, Vol. 156, No. 1, 01.1999, p. 19-26.

Research output: Contribution to journalArticle

Volkow, ND, Wang, GJ, Fowler, JS, Hitzemann, R, Angrist, B, Gatley, SJ, Logan, J, Ding, YS & Pappas, N 1999, 'Association of methylphenidate-induced craving with changes in right striato-orbitofrontal metabolism in cocaine abusers: Implications in addiction', American Journal of Psychiatry, vol. 156, no. 1, pp. 19-26.
Volkow, Nora D. ; Wang, Gene Jack ; Fowler, Joanna S. ; Hitzemann, Robert ; Angrist, Burton ; Gatley, Samuel J. ; Logan, Jean ; Ding, Yu Shin ; Pappas, Naomi. / Association of methylphenidate-induced craving with changes in right striato-orbitofrontal metabolism in cocaine abusers : Implications in addiction. In: American Journal of Psychiatry. 1999 ; Vol. 156, No. 1. pp. 19-26.
@article{e6193dc9eb844aed917e7a40c312a079,
title = "Association of methylphenidate-induced craving with changes in right striato-orbitofrontal metabolism in cocaine abusers: Implications in addiction",
abstract = "Objective: The authors have shown that decreases in dopamine D2 receptors in cocaine abusers were associated with decreased metabolism in the cingulate and prefrontal and orbitofrontal cortices. To assess whether increasing dopamine would reverse these metabolic decrements, they measured the effects of methylphenidate, a drug that increases dopamine, on brain glucose metabolism in 20 cocaine abusers. Method: The subjects underwent two [18F]fluorodeoxyglucose positron emission tomography scans, one after two sequential placebo injections and one after two intravenous doses of methylphenidate. D2 receptors were measured with [11C]raclopride to evaluate their relation to methylphenidate-induced metabolic changes. Results: Methylphenidate induced variable changes in brain metabolism: subjects with the higher D2 measures tended to increase metabolism, whereas those with the lower D2 measures tended to decrease metabolism. Methylphenidate's effects were significant for increases in metabolism in the superior cingulate, right thalamus, and cerebellum. Methylphenidate-induced changes in the right orbitofrontal cortex and right striatum were associated with craving, and those in the prefrontal cortex were associated with mood. Conclusions: Although methylphenidate increased metabolism in the superior cingulate, it only increased metabolism in orbitofrontal or prefrontal cortices in the subjects in whom it enhanced craving and mood, respectively. This indicates that dopamine enhancement is not sufficient per se to increase metabolism in these frontal regions. Activation of the right orbitofrontal cortex and right striatum (brain regions found to be abnormal in compulsive disorders) in the subjects reporting craving may be one of the mechanisms underlying compulsive drug administration in addicted persons. The predominant correlation of craving with right but not left brain regions suggests laterality of reinforcing and/or conditioned responses.",
author = "Volkow, {Nora D.} and Wang, {Gene Jack} and Fowler, {Joanna S.} and Robert Hitzemann and Burton Angrist and Gatley, {Samuel J.} and Jean Logan and Ding, {Yu Shin} and Naomi Pappas",
year = "1999",
month = "1",
language = "English (US)",
volume = "156",
pages = "19--26",
journal = "American Journal of Psychiatry",
issn = "0002-953X",
publisher = "American Psychiatric Association",
number = "1",

}

TY - JOUR

T1 - Association of methylphenidate-induced craving with changes in right striato-orbitofrontal metabolism in cocaine abusers

T2 - Implications in addiction

AU - Volkow, Nora D.

AU - Wang, Gene Jack

AU - Fowler, Joanna S.

AU - Hitzemann, Robert

AU - Angrist, Burton

AU - Gatley, Samuel J.

AU - Logan, Jean

AU - Ding, Yu Shin

AU - Pappas, Naomi

PY - 1999/1

Y1 - 1999/1

N2 - Objective: The authors have shown that decreases in dopamine D2 receptors in cocaine abusers were associated with decreased metabolism in the cingulate and prefrontal and orbitofrontal cortices. To assess whether increasing dopamine would reverse these metabolic decrements, they measured the effects of methylphenidate, a drug that increases dopamine, on brain glucose metabolism in 20 cocaine abusers. Method: The subjects underwent two [18F]fluorodeoxyglucose positron emission tomography scans, one after two sequential placebo injections and one after two intravenous doses of methylphenidate. D2 receptors were measured with [11C]raclopride to evaluate their relation to methylphenidate-induced metabolic changes. Results: Methylphenidate induced variable changes in brain metabolism: subjects with the higher D2 measures tended to increase metabolism, whereas those with the lower D2 measures tended to decrease metabolism. Methylphenidate's effects were significant for increases in metabolism in the superior cingulate, right thalamus, and cerebellum. Methylphenidate-induced changes in the right orbitofrontal cortex and right striatum were associated with craving, and those in the prefrontal cortex were associated with mood. Conclusions: Although methylphenidate increased metabolism in the superior cingulate, it only increased metabolism in orbitofrontal or prefrontal cortices in the subjects in whom it enhanced craving and mood, respectively. This indicates that dopamine enhancement is not sufficient per se to increase metabolism in these frontal regions. Activation of the right orbitofrontal cortex and right striatum (brain regions found to be abnormal in compulsive disorders) in the subjects reporting craving may be one of the mechanisms underlying compulsive drug administration in addicted persons. The predominant correlation of craving with right but not left brain regions suggests laterality of reinforcing and/or conditioned responses.

AB - Objective: The authors have shown that decreases in dopamine D2 receptors in cocaine abusers were associated with decreased metabolism in the cingulate and prefrontal and orbitofrontal cortices. To assess whether increasing dopamine would reverse these metabolic decrements, they measured the effects of methylphenidate, a drug that increases dopamine, on brain glucose metabolism in 20 cocaine abusers. Method: The subjects underwent two [18F]fluorodeoxyglucose positron emission tomography scans, one after two sequential placebo injections and one after two intravenous doses of methylphenidate. D2 receptors were measured with [11C]raclopride to evaluate their relation to methylphenidate-induced metabolic changes. Results: Methylphenidate induced variable changes in brain metabolism: subjects with the higher D2 measures tended to increase metabolism, whereas those with the lower D2 measures tended to decrease metabolism. Methylphenidate's effects were significant for increases in metabolism in the superior cingulate, right thalamus, and cerebellum. Methylphenidate-induced changes in the right orbitofrontal cortex and right striatum were associated with craving, and those in the prefrontal cortex were associated with mood. Conclusions: Although methylphenidate increased metabolism in the superior cingulate, it only increased metabolism in orbitofrontal or prefrontal cortices in the subjects in whom it enhanced craving and mood, respectively. This indicates that dopamine enhancement is not sufficient per se to increase metabolism in these frontal regions. Activation of the right orbitofrontal cortex and right striatum (brain regions found to be abnormal in compulsive disorders) in the subjects reporting craving may be one of the mechanisms underlying compulsive drug administration in addicted persons. The predominant correlation of craving with right but not left brain regions suggests laterality of reinforcing and/or conditioned responses.

UR - http://www.scopus.com/inward/record.url?scp=0032897188&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032897188&partnerID=8YFLogxK

M3 - Article

VL - 156

SP - 19

EP - 26

JO - American Journal of Psychiatry

JF - American Journal of Psychiatry

SN - 0002-953X

IS - 1

ER -