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Optical suppression of drug-evoked phasic dopamine release

Brief fluctuations in dopamine concentration (dopamine transients) play a key role in behavior towards rewards, including drugs of abuse. Drug-evoked dopamine transients may result from actions at both dopamine cell bodies and dopamine terminals. Inhibitory opsins can be targeted to dopamine neurons...

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Autores principales: McCutcheon, James E., Cone, Jackson J., Sinon, Christopher G., Fortin, Samantha M., Kantak, Pranish A., Witten, Ilana B., Deisseroth, Karl, Stuber, Garret D., Roitman, Mitchell F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4166314/
https://www.ncbi.nlm.nih.gov/pubmed/25278845
http://dx.doi.org/10.3389/fncir.2014.00114
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author McCutcheon, James E.
Cone, Jackson J.
Sinon, Christopher G.
Fortin, Samantha M.
Kantak, Pranish A.
Witten, Ilana B.
Deisseroth, Karl
Stuber, Garret D.
Roitman, Mitchell F.
author_facet McCutcheon, James E.
Cone, Jackson J.
Sinon, Christopher G.
Fortin, Samantha M.
Kantak, Pranish A.
Witten, Ilana B.
Deisseroth, Karl
Stuber, Garret D.
Roitman, Mitchell F.
author_sort McCutcheon, James E.
collection PubMed
description Brief fluctuations in dopamine concentration (dopamine transients) play a key role in behavior towards rewards, including drugs of abuse. Drug-evoked dopamine transients may result from actions at both dopamine cell bodies and dopamine terminals. Inhibitory opsins can be targeted to dopamine neurons permitting their firing activity to be suppressed. However, as dopamine transients can become uncoupled from firing, it is unknown whether optogenetic hyperpolarization at the level of the soma is able to suppress dopamine transients. Here, we used in vivo fast-scan cyclic voltammetry to record transients evoked by cocaine and raclopride in nucleus accumbens (NAc) of urethane-anesthetized rats. We targeted halorhodopsin (NpHR) specifically to dopamine cells by injecting Cre-inducible virus into ventral tegmental area (VTA) of transgenic rats that expressed Cre recombinase under control of the tyrosine hydroxylase promoter (TH-Cre(+) rats). Consistent with previous work, co-administration of cocaine and raclopride led to the generation of dopamine transients in NAc shell. Illumination of VTA with laser strongly suppressed the frequency of transients in NpHR-expressing rats, but not in control rats. Laser did not have any effect on amplitude of transients. Thus, optogenetics can effectively reduce the occurrence of drug-evoked transients and is therefore a suitable approach for studying the functional role of such transients in drug-associated behavior.
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spelling pubmed-41663142014-10-02 Optical suppression of drug-evoked phasic dopamine release McCutcheon, James E. Cone, Jackson J. Sinon, Christopher G. Fortin, Samantha M. Kantak, Pranish A. Witten, Ilana B. Deisseroth, Karl Stuber, Garret D. Roitman, Mitchell F. Front Neural Circuits Neuroscience Brief fluctuations in dopamine concentration (dopamine transients) play a key role in behavior towards rewards, including drugs of abuse. Drug-evoked dopamine transients may result from actions at both dopamine cell bodies and dopamine terminals. Inhibitory opsins can be targeted to dopamine neurons permitting their firing activity to be suppressed. However, as dopamine transients can become uncoupled from firing, it is unknown whether optogenetic hyperpolarization at the level of the soma is able to suppress dopamine transients. Here, we used in vivo fast-scan cyclic voltammetry to record transients evoked by cocaine and raclopride in nucleus accumbens (NAc) of urethane-anesthetized rats. We targeted halorhodopsin (NpHR) specifically to dopamine cells by injecting Cre-inducible virus into ventral tegmental area (VTA) of transgenic rats that expressed Cre recombinase under control of the tyrosine hydroxylase promoter (TH-Cre(+) rats). Consistent with previous work, co-administration of cocaine and raclopride led to the generation of dopamine transients in NAc shell. Illumination of VTA with laser strongly suppressed the frequency of transients in NpHR-expressing rats, but not in control rats. Laser did not have any effect on amplitude of transients. Thus, optogenetics can effectively reduce the occurrence of drug-evoked transients and is therefore a suitable approach for studying the functional role of such transients in drug-associated behavior. Frontiers Media S.A. 2014-09-17 /pmc/articles/PMC4166314/ /pubmed/25278845 http://dx.doi.org/10.3389/fncir.2014.00114 Text en Copyright © 2014 McCutcheon, Cone, Sinon, Fortin, Kantak, Witten, Deisseroth, Stuber and Roitman. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
McCutcheon, James E.
Cone, Jackson J.
Sinon, Christopher G.
Fortin, Samantha M.
Kantak, Pranish A.
Witten, Ilana B.
Deisseroth, Karl
Stuber, Garret D.
Roitman, Mitchell F.
Optical suppression of drug-evoked phasic dopamine release
title Optical suppression of drug-evoked phasic dopamine release
title_full Optical suppression of drug-evoked phasic dopamine release
title_fullStr Optical suppression of drug-evoked phasic dopamine release
title_full_unstemmed Optical suppression of drug-evoked phasic dopamine release
title_short Optical suppression of drug-evoked phasic dopamine release
title_sort optical suppression of drug-evoked phasic dopamine release
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4166314/
https://www.ncbi.nlm.nih.gov/pubmed/25278845
http://dx.doi.org/10.3389/fncir.2014.00114
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