Role for GDNF in biochemical and behavioral adaptations to drugs of abuse

被引:141
作者
Messer, CJ
Eisch, AJ
Carlezon, WA
Whisler, K
Shen, L
Wolf, DH
Westphal, H
Collins, F
Russell, DS
Nestler, EJ [1 ]
机构
[1] Yale Univ, Sch Med, Lab Mol Psychiat, New Haven, CT 06508 USA
[2] Yale Univ, Sch Med, Yale Ctr Genes & Behav, New Haven, CT 06508 USA
[3] Connecticut Mental Hlth Ctr, New Haven, CT 06508 USA
[4] NIH, Lab Mammalian Genes & Dev, Bethesda, MD 20892 USA
[5] Amgen Inc, Thousand Oaks, CA 91320 USA
关键词
D O I
10.1016/S0896-6273(00)81154-X
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The present study examined a role for GDNF in adaptations to drugs of abuse. Infusion of GDNF into the ventral tegmental area (VTA), a dopaminergic brain region important for addiction, blocks certain biochemical adaptations to chronic cocaine or morphine as well as the rewarding effects of cocaine. Conversely, responses to cocaine are enhanced in rats by intra-VTA infusion of an anti-GDNF antibody and in mice heterozygous for a null mutation in the GDNF gene. Chronic morphine or cocaine exposure decreases levels of phosphoRet, the protein kinase that mediates GDNF signaling, in the VTA. Together, these results suggest a feedback loop, whereby drugs of abuse decrease signaling through endogenous GDNF pathways in the VTA, which then increases the behavioral sensitivity to subsequent drug exposure.
引用
收藏
页码:247 / 257
页数:11
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