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

Chad J. Messer, Amelia J. Eisch, William A. Carlezon, Kim Whisler, Liya Shen, Daniel H. Wolf, Heiner Westphal, Frank Collins, David S. Russell, Eric J. Nestler

Research output: Contribution to journalArticlepeer-review

141 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)247-257
Number of pages11
Issue number1
StatePublished - 2000

ASJC Scopus subject areas

  • Neuroscience(all)


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