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

doi:10.1016/S0896-6273(00)81154-X

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

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Abstract

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 language	English (US)
Pages (from-to)	247-257
Number of pages	11
Journal	Neuron
Volume	26
Issue number	1
DOIs	https://doi.org/10.1016/S0896-6273(00)81154-X
State	Published - 2000

ASJC Scopus subject areas

General Neuroscience

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10.1016/S0896-6273(00)81154-X

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title = "Role for GDNF in biochemical and behavioral adaptations to drugs of abuse",

abstract = "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.",

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

note = "Funding Information: This work was supported by grants from the National Institute on Drug Abuse and by the Abraham Ribicoff Research Facilities of the Connecticut Mental Health Center, State of Connecticut Department of Mental Health and Addiction Services.",

year = "2000",

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T1 - Role for GDNF in biochemical and behavioral adaptations to drugs of abuse

AU - Messer, Chad J.

AU - Eisch, Amelia J.

AU - Carlezon, William A.

AU - Whisler, Kim

AU - Shen, Liya

AU - Wolf, Daniel H.

AU - Westphal, Heiner

AU - Collins, Frank

AU - Russell, David S.

AU - Nestler, Eric J.

N1 - Funding Information: This work was supported by grants from the National Institute on Drug Abuse and by the Abraham Ribicoff Research Facilities of the Connecticut Mental Health Center, State of Connecticut Department of Mental Health and Addiction Services.

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N2 - 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.

AB - 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.

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

Abstract

ASJC Scopus subject areas

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