GABAergic blockade of cocaine-associated cue-induced increases in nucleus accumbens dopamine

Madina R. Gerasimov; Wynne K. Schiffer; Eliot L. Gardner; Douglas A. Marsteller; Ian C. Lennon; Stephen J.C. Taylor; Jonathan D. Brodie; Charles R. Ashby; Stephen L. Dewey

doi:10.1016/S0014-2999(01)00800-7

GABAergic blockade of cocaine-associated cue-induced increases in nucleus accumbens dopamine

Madina R. Gerasimov
, Wynne K. Schiffer
, Eliot L. Gardner
, Douglas A. Marsteller
, Ian C. Lennon
, Stephen J.C. Taylor
, Jonathan D. Brodie
, Charles R. Ashby
, Stephen L. Dewey

Neurology

Research output: Contribution to journal › Article › peer-review

52 Scopus citations

Abstract

Environments previously associated with drug use can become one of the most common factors triggering relapse to drug-seeking behavior. To better understand the neurochemical mechanisms potentially mediating these cues, we measured nucleus accumbens dopamine levels in animals exposed to environmental cues previously paired with cocaine administration. In animals exposed to a cocaine-paired environment nucleus accumbens dopamine increased by 25%. When administered 2.5 h prior to presentation of the environmental trigger, racemic vigabatrin (an irreversible inhibitor of γ-aminobutyric acid (GABA)-transaminase) abolished this cue-induced increase. Conversely, R-(-)-vigabatrin, the inactive enantiomer, had no effect. Combined with our earlier findings, these studies support the potential therapeutic benefit of this enzyme-based GABAergic strategy to modulate brain dopamine and the subsequent treatment of drug addiction.

Original language	English (US)
Pages (from-to)	205-209
Number of pages	5
Journal	European Journal of Pharmacology
Volume	414
Issue number	2-3
DOIs	https://doi.org/10.1016/S0014-2999(01)00800-7
State	Published - Mar 2 2001

Bibliographical note

Funding Information:
The authors thank Mr. David Alexoff and Dr. Joanna Fowler for helpful discussions. This research was carried out under contract with the U.S. Department of Energy Office of Biological and Environmental Research (USDOE/OBER DE-AC02-98CH10886) and by the National Institutes of Mental Health (NIMH MH49165 and NIMH R2955155.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Cocaine
Conditioning
Contextual cue
GABA (γ-aminobutyric acid)
In vivo
Microdialysis
Vigabatrin

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10.1016/S0014-2999(01)00800-7

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title = "GABAergic blockade of cocaine-associated cue-induced increases in nucleus accumbens dopamine",

abstract = "Environments previously associated with drug use can become one of the most common factors triggering relapse to drug-seeking behavior. To better understand the neurochemical mechanisms potentially mediating these cues, we measured nucleus accumbens dopamine levels in animals exposed to environmental cues previously paired with cocaine administration. In animals exposed to a cocaine-paired environment nucleus accumbens dopamine increased by 25\%. When administered 2.5 h prior to presentation of the environmental trigger, racemic vigabatrin (an irreversible inhibitor of γ-aminobutyric acid (GABA)-transaminase) abolished this cue-induced increase. Conversely, R-(-)-vigabatrin, the inactive enantiomer, had no effect. Combined with our earlier findings, these studies support the potential therapeutic benefit of this enzyme-based GABAergic strategy to modulate brain dopamine and the subsequent treatment of drug addiction.",

keywords = "Cocaine, Conditioning, Contextual cue, GABA (γ-aminobutyric acid), In vivo, Microdialysis, Vigabatrin",

author = "Gerasimov, \{Madina R.\} and Schiffer, \{Wynne K.\} and Gardner, \{Eliot L.\} and Marsteller, \{Douglas A.\} and Lennon, \{Ian C.\} and Taylor, \{Stephen J.C.\} and Brodie, \{Jonathan D.\} and Ashby, \{Charles R.\} and Dewey, \{Stephen L.\}",

note = "Funding Information: The authors thank Mr. David Alexoff and Dr. Joanna Fowler for helpful discussions. This research was carried out under contract with the U.S. Department of Energy Office of Biological and Environmental Research (USDOE/OBER DE-AC02-98CH10886) and by the National Institutes of Mental Health (NIMH MH49165 and NIMH R2955155.",

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AU - Schiffer, Wynne K.

AU - Gardner, Eliot L.

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AU - Lennon, Ian C.

AU - Taylor, Stephen J.C.

AU - Brodie, Jonathan D.

AU - Ashby, Charles R.

AU - Dewey, Stephen L.

N1 - Funding Information: The authors thank Mr. David Alexoff and Dr. Joanna Fowler for helpful discussions. This research was carried out under contract with the U.S. Department of Energy Office of Biological and Environmental Research (USDOE/OBER DE-AC02-98CH10886) and by the National Institutes of Mental Health (NIMH MH49165 and NIMH R2955155.

PY - 2001/3/2

Y1 - 2001/3/2

N2 - Environments previously associated with drug use can become one of the most common factors triggering relapse to drug-seeking behavior. To better understand the neurochemical mechanisms potentially mediating these cues, we measured nucleus accumbens dopamine levels in animals exposed to environmental cues previously paired with cocaine administration. In animals exposed to a cocaine-paired environment nucleus accumbens dopamine increased by 25%. When administered 2.5 h prior to presentation of the environmental trigger, racemic vigabatrin (an irreversible inhibitor of γ-aminobutyric acid (GABA)-transaminase) abolished this cue-induced increase. Conversely, R-(-)-vigabatrin, the inactive enantiomer, had no effect. Combined with our earlier findings, these studies support the potential therapeutic benefit of this enzyme-based GABAergic strategy to modulate brain dopamine and the subsequent treatment of drug addiction.

AB - Environments previously associated with drug use can become one of the most common factors triggering relapse to drug-seeking behavior. To better understand the neurochemical mechanisms potentially mediating these cues, we measured nucleus accumbens dopamine levels in animals exposed to environmental cues previously paired with cocaine administration. In animals exposed to a cocaine-paired environment nucleus accumbens dopamine increased by 25%. When administered 2.5 h prior to presentation of the environmental trigger, racemic vigabatrin (an irreversible inhibitor of γ-aminobutyric acid (GABA)-transaminase) abolished this cue-induced increase. Conversely, R-(-)-vigabatrin, the inactive enantiomer, had no effect. Combined with our earlier findings, these studies support the potential therapeutic benefit of this enzyme-based GABAergic strategy to modulate brain dopamine and the subsequent treatment of drug addiction.

KW - Cocaine

KW - Conditioning

KW - Contextual cue

KW - GABA (γ-aminobutyric acid)

KW - In vivo

KW - Microdialysis

KW - Vigabatrin

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ER -

GABAergic blockade of cocaine-associated cue-induced increases in nucleus accumbens dopamine

Abstract

Bibliographical note

UN SDGs

Keywords

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