Targeted disruption of cocaine-activated nucleus accumbens neurons prevents context-specific sensitization

Eisuke Koya; Sam A. Golden; Brandon K. Harvey; Danielle H. Guez-Barber; Alexander Berkow; Danielle E. Simmons; Jennifer M. Bossert; Sunila G. Nair; Jamie L. Uejima; Marcelo T. Marin; Timothy B. Mitchell; David Farquhar; Sukhen C. Ghosh; Brandi J. Mattson; Bruce T. Hope

doi:10.1038/nn.2364

Targeted disruption of cocaine-activated nucleus accumbens neurons prevents context-specific sensitization

Eisuke Koya, Sam A. Golden, Brandon K. Harvey, Danielle H. Guez-Barber, Alexander Berkow, Danielle E. Simmons, Jennifer M. Bossert, Sunila G. Nair, Jamie L. Uejima, Marcelo T. Marin, Timothy B. Mitchell, David Farquhar, Sukhen C. Ghosh, Brandi J. Mattson, Bruce T. Hope

Anesthesiology

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

222 Scopus citations

Abstract

Learned associations between effects of abused drugs and the drug administration environment are important in drug addiction. Histochemical and electrophysiological studies suggest that these associations are encoded in sparsely distributed nucleus accumbens neurons that are selectively activated by drugs and drug-associated cues. Although correlations have been observed between nucleus accumbens neuronal activity and responsivity to drugs and drug cues, no technique exists for selectively manipulating these activated neurons and establishing their causal role in behavioral effects of drugs and drug cues. Here we describe a new approach, which we term the 'Daun02 inactivation method', that selectively inactivates a minority of neurons previously activated by cocaine in an environment repeatedly paired with cocaine to demonstrate a causal role for these activated neurons in context-specific cocaine-induced psychomotor sensitization in rats. This method provides a new tool for studying the causal roles of selectively activated neurons in behavioral effects of drugs and drug cues and in other learned behaviors.

Original language	English (US)
Pages (from-to)	1069-1073
Number of pages	5
Journal	Nature neuroscience
Volume	12
Issue number	8
DOIs	https://doi.org/10.1038/nn.2364
State	Published - Aug 2009

Funding

This research was supported by the Intramural Research Program of the National Institute on Drug Abuse. We thank E. Wentzell for her excellent editorial assistance, K. Knestaut for breeding the cfos-lacZ rats and T. Adams-Deutsch, C. Pickens and K. Wihbey for technical assistance. We are especially thankful to Y. Shaham for his comments over the years and for his help in writing this manuscript, and to R. Wise for providing the inspiration for this study.

ASJC Scopus subject areas

General Neuroscience

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

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10.1038/nn.2364

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Koya, E., Golden, S. A., Harvey, B. K., Guez-Barber, D. H., Berkow, A., Simmons, D. E., Bossert, J. M., Nair, S. G., Uejima, J. L., Marin, M. T., Mitchell, T. B., Farquhar, D., Ghosh, S. C., Mattson, B. J., & Hope, B. T. (2009). Targeted disruption of cocaine-activated nucleus accumbens neurons prevents context-specific sensitization. Nature neuroscience, 12(8), 1069-1073. https://doi.org/10.1038/nn.2364

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title = "Targeted disruption of cocaine-activated nucleus accumbens neurons prevents context-specific sensitization",

abstract = "Learned associations between effects of abused drugs and the drug administration environment are important in drug addiction. Histochemical and electrophysiological studies suggest that these associations are encoded in sparsely distributed nucleus accumbens neurons that are selectively activated by drugs and drug-associated cues. Although correlations have been observed between nucleus accumbens neuronal activity and responsivity to drugs and drug cues, no technique exists for selectively manipulating these activated neurons and establishing their causal role in behavioral effects of drugs and drug cues. Here we describe a new approach, which we term the 'Daun02 inactivation method', that selectively inactivates a minority of neurons previously activated by cocaine in an environment repeatedly paired with cocaine to demonstrate a causal role for these activated neurons in context-specific cocaine-induced psychomotor sensitization in rats. This method provides a new tool for studying the causal roles of selectively activated neurons in behavioral effects of drugs and drug cues and in other learned behaviors.",

author = "Eisuke Koya and Golden, {Sam A.} and Harvey, {Brandon K.} and Guez-Barber, {Danielle H.} and Alexander Berkow and Simmons, {Danielle E.} and Bossert, {Jennifer M.} and Nair, {Sunila G.} and Uejima, {Jamie L.} and Marin, {Marcelo T.} and Mitchell, {Timothy B.} and David Farquhar and Ghosh, {Sukhen C.} and Mattson, {Brandi J.} and Hope, {Bruce T.}",

note = "Funding Information: This research was supported by the Intramural Research Program of the National Institute on Drug Abuse. We thank E. Wentzell for her excellent editorial assistance, K. Knestaut for breeding the cfos-lacZ rats and T. Adams-Deutsch, C. Pickens and K. Wihbey for technical assistance. We are especially thankful to Y. Shaham for his comments over the years and for his help in writing this manuscript, and to R. Wise for providing the inspiration for this study.",

year = "2009",

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doi = "10.1038/nn.2364",

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Koya, E, Golden, SA, Harvey, BK, Guez-Barber, DH, Berkow, A, Simmons, DE, Bossert, JM, Nair, SG, Uejima, JL, Marin, MT, Mitchell, TB, Farquhar, D, Ghosh, SC, Mattson, BJ & Hope, BT 2009, 'Targeted disruption of cocaine-activated nucleus accumbens neurons prevents context-specific sensitization', Nature neuroscience, vol. 12, no. 8, pp. 1069-1073. https://doi.org/10.1038/nn.2364

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T1 - Targeted disruption of cocaine-activated nucleus accumbens neurons prevents context-specific sensitization

AU - Koya, Eisuke

AU - Golden, Sam A.

AU - Harvey, Brandon K.

AU - Guez-Barber, Danielle H.

AU - Berkow, Alexander

AU - Simmons, Danielle E.

AU - Bossert, Jennifer M.

AU - Nair, Sunila G.

AU - Uejima, Jamie L.

AU - Marin, Marcelo T.

AU - Mitchell, Timothy B.

AU - Farquhar, David

AU - Ghosh, Sukhen C.

AU - Mattson, Brandi J.

AU - Hope, Bruce T.

N1 - Funding Information: This research was supported by the Intramural Research Program of the National Institute on Drug Abuse. We thank E. Wentzell for her excellent editorial assistance, K. Knestaut for breeding the cfos-lacZ rats and T. Adams-Deutsch, C. Pickens and K. Wihbey for technical assistance. We are especially thankful to Y. Shaham for his comments over the years and for his help in writing this manuscript, and to R. Wise for providing the inspiration for this study.

PY - 2009/8

Y1 - 2009/8

N2 - Learned associations between effects of abused drugs and the drug administration environment are important in drug addiction. Histochemical and electrophysiological studies suggest that these associations are encoded in sparsely distributed nucleus accumbens neurons that are selectively activated by drugs and drug-associated cues. Although correlations have been observed between nucleus accumbens neuronal activity and responsivity to drugs and drug cues, no technique exists for selectively manipulating these activated neurons and establishing their causal role in behavioral effects of drugs and drug cues. Here we describe a new approach, which we term the 'Daun02 inactivation method', that selectively inactivates a minority of neurons previously activated by cocaine in an environment repeatedly paired with cocaine to demonstrate a causal role for these activated neurons in context-specific cocaine-induced psychomotor sensitization in rats. This method provides a new tool for studying the causal roles of selectively activated neurons in behavioral effects of drugs and drug cues and in other learned behaviors.

AB - Learned associations between effects of abused drugs and the drug administration environment are important in drug addiction. Histochemical and electrophysiological studies suggest that these associations are encoded in sparsely distributed nucleus accumbens neurons that are selectively activated by drugs and drug-associated cues. Although correlations have been observed between nucleus accumbens neuronal activity and responsivity to drugs and drug cues, no technique exists for selectively manipulating these activated neurons and establishing their causal role in behavioral effects of drugs and drug cues. Here we describe a new approach, which we term the 'Daun02 inactivation method', that selectively inactivates a minority of neurons previously activated by cocaine in an environment repeatedly paired with cocaine to demonstrate a causal role for these activated neurons in context-specific cocaine-induced psychomotor sensitization in rats. This method provides a new tool for studying the causal roles of selectively activated neurons in behavioral effects of drugs and drug cues and in other learned behaviors.

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Targeted disruption of cocaine-activated nucleus accumbens neurons prevents context-specific sensitization

Abstract

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UN SDGs

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