 |
The Journal of Neuroscience, June 14, 2006, 26(24):6583-6588; doi:10.1523/JNEUROSCI.1544-06.2006
Previous Article | Next Article 
Brief Communications
Cocaine Cues and Dopamine in Dorsal Striatum: Mechanism of Craving in Cocaine Addiction
Nora D. Volkow,1
Gene-Jack Wang,2
Frank Telang,1
Joanna S. Fowler,3
Jean Logan,3
Anna-Rose Childress,4
Millard Jayne,1
Yeming Ma,1 and
Christopher Wong3
1National Institute on Alcohol Abuse and Alcoholism, Bethesda Maryland 20892, 2Medical Department and 3Department of Chemistry, Brookhaven National Laboratory, Upton, New York 11973, and 4Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104
Correspondence should be addressed to Dr. Nora D Volkow, National Institute on Drug Abuse, 6001 Executive Boulevard, Room 5274, Bethesda, MD 20892. Email: nvolkow{at}nida.nih.gov
The ability of drugs of abuse to increase dopamine in nucleus accumbens underlies their reinforcing effects. However, preclinical studies have shown that with repeated drug exposure neutral stimuli paired with the drug (conditioned stimuli) start to increase dopamine by themselves, which is an effect that could underlie drug-seeking behavior. Here we test whether dopamine increases occur to conditioned stimuli in human subjects addicted to cocaine and whether this is associated with drug craving. We tested eighteen cocaine-addicted subjects using positron emission tomography and [11C]raclopride (dopamine D2 receptor radioligand sensitive to competition with endogenous dopamine). We measured changes in dopamine by comparing the specific binding of [11C]raclopride when subjects watched a neutral video (nature scenes) versus when they watched a cocaine-cue video (scenes of subjects smoking cocaine). The specific binding of [11C]raclopride in dorsal (caudate and putamen) but not in ventral striatum (in which nucleus accumbens is located) was significantly reduced in the cocaine-cue condition and the magnitude of this reduction correlated with self-reports of craving. Moreover, subjects with the highest scores on measures of withdrawal symptoms and of addiction severity that have been shown to predict treatment outcomes, had the largest dopamine changes in dorsal striatum. This provides evidence that dopamine in the dorsal striatum (region implicated in habit learning and in action initiation) is involved with craving and is a fundamental component of addiction. Because craving is a key contributor to relapse, strategies aimed at inhibiting dopamine increases from conditioned responses are likely to be therapeutically beneficial in cocaine addiction.
Key words: imaging; raclopride; addiction; caudate; putamen; conditioned responses; D2 receptors
Received April 10, 2006;
revised May 8, 2006;
accepted May 14, 2006.
Correspondence should be addressed to Dr. Nora D Volkow, National Institute on Drug Abuse, 6001 Executive Boulevard, Room 5274, Bethesda, MD 20892. Email: nvolkow{at}nida.nih.gov
This article has been cited by other articles:

|
 |

|
 |
 
W. K. Schiffer, C. N. B. Liebling, C. Reiszel, J. M. Hooker, J. D. Brodie, and S. L. Dewey
Cue-Induced Dopamine Release Predicts Cocaine Preference: Positron Emission Tomography Studies in Freely Moving Rodents
J. Neurosci.,
May 13, 2009;
29(19):
6176 - 6185.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. Z. Goldstein, D. Tomasi, N. Alia-Klein, J. Honorio Carrillo, T. Maloney, P. A. Woicik, R. Wang, F. Telang, and N. D. Volkow
Dopaminergic Response to Drug Words in Cocaine Addiction
J. Neurosci.,
May 6, 2009;
29(18):
6001 - 6006.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. D. L. Steeves, J. Miyasaki, M. Zurowski, A. E. Lang, G. Pellecchia, T. Van Eimeren, P. Rusjan, S. Houle, and A. P. Strafella
Increased striatal dopamine release in Parkinsonian patients with pathological gambling: a [11C] raclopride PET study
Brain,
May 1, 2009;
132(5):
1376 - 1385.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Gabriele, B. Setlow, and M. G. Packard
Cocaine self-administration alters the relative effectiveness of multiple memory systems during extinction
Learn. Mem.,
April 23, 2009;
16(5):
296 - 299.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Yalachkov, J. Kaiser, and M. J. Naumer
Brain Regions Related to Tool Use and Action Knowledge Reflect Nicotine Dependence
J. Neurosci.,
April 15, 2009;
29(15):
4922 - 4929.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
O. A. van den Heuvel, P. L. Remijnse, D. Mataix-Cols, H. Vrenken, H. J. Groenewegen, H. B. M. Uylings, A. J. L. M. van Balkom, and D. J. Veltman
The major symptom dimensions of obsessive-compulsive disorder are mediated by partially distinct neural systems
Brain,
April 1, 2009;
132(4):
853 - 868.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. K. Chandler, B. W. Fletcher, and N. D. Volkow
Treating Drug Abuse and Addiction in the Criminal Justice System: Improving Public Health and Safety
JAMA,
January 14, 2009;
301(2):
183 - 190.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. J Everitt, D. Belin, D. Economidou, Y. Pelloux, J. W Dalley, and T. W Robbins
Neural mechanisms underlying the vulnerability to develop compulsive drug-seeking habits and addiction
Phil Trans R Soc B,
October 12, 2008;
363(1507):
3125 - 3135.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. D Volkow, G.-J. Wang, J. S Fowler, and F. Telang
Overlapping neuronal circuits in addiction and obesity: evidence of systems pathology
Phil Trans R Soc B,
October 12, 2008;
363(1507):
3191 - 3200.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. H. Corbit and P. H. Janak
Inactivation of the Lateral But Not Medial Dorsal Striatum Eliminates the Excitatory Impact of Pavlovian Stimuli on Instrumental Responding
J. Neurosci.,
December 19, 2007;
27(51):
13977 - 13981.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. D. Volkow, J. S. Fowler, G.-J. Wang, J. M. Swanson, and F. Telang
Dopamine in Drug Abuse and Addiction: Results of Imaging Studies and Treatment Implications
Arch Neurol,
November 1, 2007;
64(11):
1575 - 1579.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
I. Boileau, A. Dagher, M. Leyton, K. Welfeld, L. Booij, M. Diksic, and C. Benkelfat
Conditioned Dopamine Release in Humans: A Positron Emission Tomography [11C]Raclopride Study with Amphetamine
J. Neurosci.,
April 11, 2007;
27(15):
3998 - 4003.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. J. Day and R. M. Carelli
The Nucleus Accumbens and Pavlovian Reward Learning
Neuroscientist,
April 1, 2007;
13(2):
148 - 159.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Wang, S. Carnicella, K. Phamluong, J. Jeanblanc, J. A. Ronesi, N. Chaudhri, P. H. Janak, D. M. Lovinger, and D. Ron
Ethanol Induces Long-Term Facilitation of NR2B-NMDA Receptor Activity in the Dorsal Striatum: Implications for Alcohol Drinking Behavior
J. Neurosci.,
March 28, 2007;
27(13):
3593 - 3602.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|