Loss of Feedback Inhibition via D2 Autoreceptors Enhances Acquisition of Cocaine Taking and Reactivity to Drug-Paired Cues

A prominent aspect of drug addiction is the ability of drug-associated cues to elicit craving and facilitate relapse. Understanding the factors that regulate cue reactivity will be vital for improving treatment of addictive disorders. Low availability of dopamine (DA) D2 receptors (D2Rs) in the stri...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Adrover, Martín F., Rubinstein, Marcelo
Publicado:	2015
Materias:	autoreceptor cocaine dopamine dopamine 2 receptor dopamine uptake inhibitor DRD2 protein, mouse animal association cocaine dependence disease model drug effects drug self administration feedback system genetics instrumental conditioning knockout mouse male mesencephalon metabolism nerve cell nerve cell inhibition physiology Animals Autoreceptors Cocaine Cocaine-Related Disorders Conditioning, Operant Cues Disease Models, Animal Dopamine Dopamine Uptake Inhibitors Feedback, Physiological Male Mesencephalon Mice, Knockout Neural Inhibition Neurons Receptors, Dopamine D2 Self Administration
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0893133X_v40_n6_p1495_Holroyd http://hdl.handle.net/20.500.12110/paper_0893133X_v40_n6_p1495_Holroyd
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_0893133X_v40_n6_p1495_Holroyd
record_format	dspace
spelling	paper:paper_0893133X_v40_n6_p1495_Holroyd2025-07-30T18:23:51Z Loss of Feedback Inhibition via D2 Autoreceptors Enhances Acquisition of Cocaine Taking and Reactivity to Drug-Paired Cues Adrover, Martín F. Rubinstein, Marcelo autoreceptor cocaine dopamine dopamine 2 receptor dopamine uptake inhibitor DRD2 protein, mouse animal association cocaine dependence disease model drug effects drug self administration feedback system genetics instrumental conditioning knockout mouse male mesencephalon metabolism nerve cell nerve cell inhibition physiology Animals Autoreceptors Cocaine Cocaine-Related Disorders Conditioning, Operant Cues Disease Models, Animal Dopamine Dopamine Uptake Inhibitors Feedback, Physiological Male Mesencephalon Mice, Knockout Neural Inhibition Neurons Receptors, Dopamine D2 Self Administration A prominent aspect of drug addiction is the ability of drug-associated cues to elicit craving and facilitate relapse. Understanding the factors that regulate cue reactivity will be vital for improving treatment of addictive disorders. Low availability of dopamine (DA) D2 receptors (D2Rs) in the striatum is associated with high cocaine intake and compulsive use. However, the role of D2Rs of nonstriatal origin in cocaine seeking and taking behavior and cue reactivity is less understood and possibly underestimated. D2Rs expressed by midbrain DA neurons function as autoreceptors, exerting inhibitory feedback on DA synthesis and release. Here, we show that selective loss of D2 autoreceptors impairs the feedback inhibition of DA release and amplifies the effect of cocaine on DA transmission in the nucleus accumbens (NAc) in vitro. Mice lacking D2 autoreceptors acquire a cued-operant self-administration task for cocaine faster than littermate control mice but acquire similarly for a natural reward. Furthermore, although mice lacking D2 autoreceptors were able to extinguish self-administration behavior in the absence of cocaine and paired cues, they exhibited perseverative responding when cocaine-paired cues were present. This enhanced cue reactivity was selective for cocaine and was not seen during extinction of sucrose self-administration. We conclude that low levels of D2 autoreceptors enhance the salience of cocaine-paired cues and can contribute to the vulnerability for cocaine use and relapse. © 2015 American College of Neuropsychopharmacology. All rights reserved. Fil:Adrover, M.F. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Rubinstein, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2015 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0893133X_v40_n6_p1495_Holroyd http://hdl.handle.net/20.500.12110/paper_0893133X_v40_n6_p1495_Holroyd
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	autoreceptor cocaine dopamine dopamine 2 receptor dopamine uptake inhibitor DRD2 protein, mouse animal association cocaine dependence disease model drug effects drug self administration feedback system genetics instrumental conditioning knockout mouse male mesencephalon metabolism nerve cell nerve cell inhibition physiology Animals Autoreceptors Cocaine Cocaine-Related Disorders Conditioning, Operant Cues Disease Models, Animal Dopamine Dopamine Uptake Inhibitors Feedback, Physiological Male Mesencephalon Mice, Knockout Neural Inhibition Neurons Receptors, Dopamine D2 Self Administration
spellingShingle	autoreceptor cocaine dopamine dopamine 2 receptor dopamine uptake inhibitor DRD2 protein, mouse animal association cocaine dependence disease model drug effects drug self administration feedback system genetics instrumental conditioning knockout mouse male mesencephalon metabolism nerve cell nerve cell inhibition physiology Animals Autoreceptors Cocaine Cocaine-Related Disorders Conditioning, Operant Cues Disease Models, Animal Dopamine Dopamine Uptake Inhibitors Feedback, Physiological Male Mesencephalon Mice, Knockout Neural Inhibition Neurons Receptors, Dopamine D2 Self Administration Adrover, Martín F. Rubinstein, Marcelo Loss of Feedback Inhibition via D2 Autoreceptors Enhances Acquisition of Cocaine Taking and Reactivity to Drug-Paired Cues
topic_facet	autoreceptor cocaine dopamine dopamine 2 receptor dopamine uptake inhibitor DRD2 protein, mouse animal association cocaine dependence disease model drug effects drug self administration feedback system genetics instrumental conditioning knockout mouse male mesencephalon metabolism nerve cell nerve cell inhibition physiology Animals Autoreceptors Cocaine Cocaine-Related Disorders Conditioning, Operant Cues Disease Models, Animal Dopamine Dopamine Uptake Inhibitors Feedback, Physiological Male Mesencephalon Mice, Knockout Neural Inhibition Neurons Receptors, Dopamine D2 Self Administration
description	A prominent aspect of drug addiction is the ability of drug-associated cues to elicit craving and facilitate relapse. Understanding the factors that regulate cue reactivity will be vital for improving treatment of addictive disorders. Low availability of dopamine (DA) D2 receptors (D2Rs) in the striatum is associated with high cocaine intake and compulsive use. However, the role of D2Rs of nonstriatal origin in cocaine seeking and taking behavior and cue reactivity is less understood and possibly underestimated. D2Rs expressed by midbrain DA neurons function as autoreceptors, exerting inhibitory feedback on DA synthesis and release. Here, we show that selective loss of D2 autoreceptors impairs the feedback inhibition of DA release and amplifies the effect of cocaine on DA transmission in the nucleus accumbens (NAc) in vitro. Mice lacking D2 autoreceptors acquire a cued-operant self-administration task for cocaine faster than littermate control mice but acquire similarly for a natural reward. Furthermore, although mice lacking D2 autoreceptors were able to extinguish self-administration behavior in the absence of cocaine and paired cues, they exhibited perseverative responding when cocaine-paired cues were present. This enhanced cue reactivity was selective for cocaine and was not seen during extinction of sucrose self-administration. We conclude that low levels of D2 autoreceptors enhance the salience of cocaine-paired cues and can contribute to the vulnerability for cocaine use and relapse. © 2015 American College of Neuropsychopharmacology. All rights reserved.
author	Adrover, Martín F. Rubinstein, Marcelo
author_facet	Adrover, Martín F. Rubinstein, Marcelo
author_sort	Adrover, Martín F.
title	Loss of Feedback Inhibition via D2 Autoreceptors Enhances Acquisition of Cocaine Taking and Reactivity to Drug-Paired Cues
title_short	Loss of Feedback Inhibition via D2 Autoreceptors Enhances Acquisition of Cocaine Taking and Reactivity to Drug-Paired Cues
title_full	Loss of Feedback Inhibition via D2 Autoreceptors Enhances Acquisition of Cocaine Taking and Reactivity to Drug-Paired Cues
title_fullStr	Loss of Feedback Inhibition via D2 Autoreceptors Enhances Acquisition of Cocaine Taking and Reactivity to Drug-Paired Cues
title_full_unstemmed	Loss of Feedback Inhibition via D2 Autoreceptors Enhances Acquisition of Cocaine Taking and Reactivity to Drug-Paired Cues
title_sort	loss of feedback inhibition via d2 autoreceptors enhances acquisition of cocaine taking and reactivity to drug-paired cues
publishDate	2015
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0893133X_v40_n6_p1495_Holroyd http://hdl.handle.net/20.500.12110/paper_0893133X_v40_n6_p1495_Holroyd
work_keys_str_mv	AT adrovermartinf lossoffeedbackinhibitionviad2autoreceptorsenhancesacquisitionofcocainetakingandreactivitytodrugpairedcues AT rubinsteinmarcelo lossoffeedbackinhibitionviad2autoreceptorsenhancesacquisitionofcocainetakingandreactivitytodrugpairedcues
_version_	1840321783248453632

Loss of Feedback Inhibition via D2 Autoreceptors Enhances Acquisition of Cocaine Taking and Reactivity to Drug-Paired Cues

Ejemplares similares