Synaptic plasticity in the mesolimbic dopamine system

被引:91
作者
Thomas, MJ
Malenka, RC [1 ]
机构
[1] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Nancy Friend Pritzker Lab, Palo Alto, CA 94304 USA
[2] Univ Minnesota, Dept Neurosci, Minneapolis, MN 55455 USA
[3] Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA
[4] Univ Minnesota, Inst Human Genet, Minneapolis, MN 55455 USA
关键词
addiction; dopamine; drugs of abuse; nucleus accumbens; ventral tegmental area;
D O I
10.1098/rstb.2002.1236
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Long-term potentiation (LTP) and long-term depression (LTD) are thought to be critical mechanisms that contribute to the neural circuit modifications that mediate all forms of experience-dependent plasticity. It has, however, been difficult to demonstrate directly that experience causes long-lasting changes in synaptic strength and that these mediate changes in behaviour. To address these potential functional roles of LTP and LTD, we have taken advantage of the powerful in vivo effects of drugs of abuse that exert their behavioural effects in large part by acting in the nucleus accumbens (NAc) and ventral tegmental area (VTA); the two major components of the mesolimbic dopamine system. Our studies suggest that in vivo drugs of abuse such as cocaine cause long-lasting changes at excitatory synapses in the NAc and VTA owing to activation of the mechanisms that underlie LTP and LTD in these structures. Thus, administration of drugs of abuse provides a distinctive model for further investigating the mechanisms and functions of synaptic plasticity in brain regions that play important roles in the control of motivated behaviour, and one with considerable practical implications.
引用
收藏
页码:815 / 819
页数:5
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