Decreased striatal dopaminergic responsiveness in detoxified cocaine-dependent subjects

被引:637
作者
Volkow, ND
Wang, GJ
Fowler, JS
Logan, J
Gatley, SJ
Hitzemann, R
Chen, AD
Dewey, SL
Pappas, N
机构
[1] BROOKHAVEN NATL LAB, DEPT CHEM, UPTON, NY 11973 USA
[2] SUNY STONY BROOK, DEPT PSYCHIAT, STONY BROOK, NY 11794 USA
关键词
D O I
10.1038/386830a0
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Cocaine blocks the reuptake of dopamine, a neurotransmitter involved in the control of movement, cognition, motivation and reward. This leads to an increase in extracellular dopamine; the reinforcing effect of cocaine is associated with elevated dopamine levels in the nucleus accumbens(1,2). But addiction to cocaine involves other effects, such as craving, loss of control and compulsive drug intake; the role of the dopamine system in these effects is less well-understood. We therefore used positron emission tomography (PET) to compare the responses of cocaine addicts and normal controls to intravenous methylphenidate, a drug that, like cocaine, causes an increase in synaptic dopamine(3). Addicts showed reduced dopamine release in the striatum, the brain region where the nucleus accumbens is located, and also had a reduced 'high' relative to controls. In contrast, addicts showed an increased response to methylphenidate in the thalamus (a region that conveys sensory input to the cortex). This thalamic response was associated with cocaine craving and was not seen in control subjects. Thus, our findings challenge the notion that addiction involves an enhanced striatal dopamine response to cocaine and/or an enhanced induction of euphoria. Moreover, they suggest a participation of thalamic dopamine pathways in cocaine addiction, a possibility that merits further investigation.
引用
收藏
页码:830 / 833
页数:4
相关论文
共 31 条
[1]  
BERGMAN J, 1989, J PHARMACOL EXP THER, V251, P150
[2]  
BROWN EE, 1992, J NEUROSCI, V12, P4112
[3]   NEW CONCEPTS IN COCAINE ADDICTION - THE DOPAMINE DEPLETION HYPOTHESIS [J].
DACKIS, CA ;
GOLD, MS .
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS, 1985, 9 (03) :469-477
[4]   STRIATAL BINDING OF THE PET LIGAND C-11 RACLOPRIDE IS ALTERED BY DRUGS THAT MODIFY SYNAPTIC DOPAMINE LEVELS [J].
DEWEY, SL ;
SMITH, GS ;
LOGAN, J ;
BRODIE, JD ;
FOWLER, JS ;
WOLF, AP .
SYNAPSE, 1993, 13 (04) :350-356
[5]  
DICHIARA G, 1988, P NATL ACAD SCI USA, V85, P5274
[6]  
GAWIN FH, 1986, ARCH GEN PSYCHIAT, V43, P107
[7]  
Gifford AN, 1996, SYNAPSE, V22, P232, DOI 10.1002/(SICI)1098-2396(199603)22:3<232::AID-SYN5>3.0.CO
[8]  
2-D
[10]  
INSEL TR, 1992, ARCH GEN PSYCHIAT, V49, P739