Cocaine supersensitivity and enhanced motivation for reward in mice lacking dopamine D2 autoreceptors

Dopamine (DA) D2 receptors expressed in DA neurons (D 2 autoreceptors) exert a negative feedback regulation that reduces DA neuron firing, DA synthesis and DA release. As D2 receptors are mostly expressed in postsynaptic neurons, pharmacological and genetic approaches have been unable to definitivel...

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Autores principales:	Bello Gay, Estefanía Pilar, Gelman, Diego Matías, Noaín, Daniela María Clara, Rubinstein, Marcelo
Publicado:	2011
Materias:	cocaine dopamine 2 receptor dopamine autoreceptor article dopaminergic nerve cell feeding behavior motivation motor performance nerve cell inhibition neurotransmission priority journal psychomotor activity supersensitivity synapse Analysis of Variance Animals Autoradiography Baclofen Choice Behavior Cocaine Conditioning, Operant Dihydroxyphenylalanine Dopamine Dopamine Agonists Dopamine Antagonists Dopamine Uptake Inhibitors Drug Interactions Enzyme Inhibitors Exploratory Behavior Food GABA-B Receptor Agonists Hydrazines Hyperkinesis Maze Learning Membrane Potentials Mesencephalon Mice Mice, Knockout Motivation Motor Activity Neurons Quinpirole Receptors, Dopamine D2 Reinforcement Schedule Reward Sulpiride
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10976256_v14_n8_p1033_Bello http://hdl.handle.net/20.500.12110/paper_10976256_v14_n8_p1033_Bello
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_10976256_v14_n8_p1033_Bello
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spelling	paper:paper_10976256_v14_n8_p1033_Bello2025-07-30T18:42:59Z Cocaine supersensitivity and enhanced motivation for reward in mice lacking dopamine D2 autoreceptors Bello Gay, Estefanía Pilar Gelman, Diego Matías Noaín, Daniela María Clara Rubinstein, Marcelo cocaine dopamine 2 receptor dopamine autoreceptor article dopaminergic nerve cell feeding behavior motivation motor performance nerve cell inhibition neurotransmission priority journal psychomotor activity supersensitivity synapse Analysis of Variance Animals Autoradiography Baclofen Choice Behavior Cocaine Conditioning, Operant Dihydroxyphenylalanine Dopamine Dopamine Agonists Dopamine Antagonists Dopamine Uptake Inhibitors Drug Interactions Enzyme Inhibitors Exploratory Behavior Food GABA-B Receptor Agonists Hydrazines Hyperkinesis Maze Learning Membrane Potentials Mesencephalon Mice Mice, Knockout Motivation Motor Activity Neurons Quinpirole Receptors, Dopamine D2 Reinforcement Schedule Reward Sulpiride Dopamine (DA) D2 receptors expressed in DA neurons (D 2 autoreceptors) exert a negative feedback regulation that reduces DA neuron firing, DA synthesis and DA release. As D2 receptors are mostly expressed in postsynaptic neurons, pharmacological and genetic approaches have been unable to definitively address the in vivo contribution of D 2 autoreceptors to DA-mediated behaviors. We found that midbrain DA neurons from mice deficient in D2 autoreceptors (Drd2 loxP/loxP; Dat+/IREScre, referred to as autoDrd2KO mice) lacked DA-mediated somatodendritic synaptic responses and inhibition of DA release. AutoDrd2KO mice displayed elevated DA synthesis and release, hyperlocomotion and supersensitivity to the psychomotor effects of cocaine. The mice also exhibited increased place preference for cocaine and enhanced motivation for food reward. Our results highlight the importance of D 2 autoreceptors in the regulation of DA neurotransmission and demonstrate that D2 autoreceptors are important for normal motor function, food-seeking behavior, and sensitivity to the locomotor and rewarding properties of cocaine. © 2011 Nature America, Inc. All rights reserved. Fil:Bello, E.P. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Gelman, D.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Noaín, D. 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. 2011 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10976256_v14_n8_p1033_Bello http://hdl.handle.net/20.500.12110/paper_10976256_v14_n8_p1033_Bello
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	cocaine dopamine 2 receptor dopamine autoreceptor article dopaminergic nerve cell feeding behavior motivation motor performance nerve cell inhibition neurotransmission priority journal psychomotor activity supersensitivity synapse Analysis of Variance Animals Autoradiography Baclofen Choice Behavior Cocaine Conditioning, Operant Dihydroxyphenylalanine Dopamine Dopamine Agonists Dopamine Antagonists Dopamine Uptake Inhibitors Drug Interactions Enzyme Inhibitors Exploratory Behavior Food GABA-B Receptor Agonists Hydrazines Hyperkinesis Maze Learning Membrane Potentials Mesencephalon Mice Mice, Knockout Motivation Motor Activity Neurons Quinpirole Receptors, Dopamine D2 Reinforcement Schedule Reward Sulpiride
spellingShingle	cocaine dopamine 2 receptor dopamine autoreceptor article dopaminergic nerve cell feeding behavior motivation motor performance nerve cell inhibition neurotransmission priority journal psychomotor activity supersensitivity synapse Analysis of Variance Animals Autoradiography Baclofen Choice Behavior Cocaine Conditioning, Operant Dihydroxyphenylalanine Dopamine Dopamine Agonists Dopamine Antagonists Dopamine Uptake Inhibitors Drug Interactions Enzyme Inhibitors Exploratory Behavior Food GABA-B Receptor Agonists Hydrazines Hyperkinesis Maze Learning Membrane Potentials Mesencephalon Mice Mice, Knockout Motivation Motor Activity Neurons Quinpirole Receptors, Dopamine D2 Reinforcement Schedule Reward Sulpiride Bello Gay, Estefanía Pilar Gelman, Diego Matías Noaín, Daniela María Clara Rubinstein, Marcelo Cocaine supersensitivity and enhanced motivation for reward in mice lacking dopamine D2 autoreceptors
topic_facet	cocaine dopamine 2 receptor dopamine autoreceptor article dopaminergic nerve cell feeding behavior motivation motor performance nerve cell inhibition neurotransmission priority journal psychomotor activity supersensitivity synapse Analysis of Variance Animals Autoradiography Baclofen Choice Behavior Cocaine Conditioning, Operant Dihydroxyphenylalanine Dopamine Dopamine Agonists Dopamine Antagonists Dopamine Uptake Inhibitors Drug Interactions Enzyme Inhibitors Exploratory Behavior Food GABA-B Receptor Agonists Hydrazines Hyperkinesis Maze Learning Membrane Potentials Mesencephalon Mice Mice, Knockout Motivation Motor Activity Neurons Quinpirole Receptors, Dopamine D2 Reinforcement Schedule Reward Sulpiride
description	Dopamine (DA) D2 receptors expressed in DA neurons (D 2 autoreceptors) exert a negative feedback regulation that reduces DA neuron firing, DA synthesis and DA release. As D2 receptors are mostly expressed in postsynaptic neurons, pharmacological and genetic approaches have been unable to definitively address the in vivo contribution of D 2 autoreceptors to DA-mediated behaviors. We found that midbrain DA neurons from mice deficient in D2 autoreceptors (Drd2 loxP/loxP; Dat+/IREScre, referred to as autoDrd2KO mice) lacked DA-mediated somatodendritic synaptic responses and inhibition of DA release. AutoDrd2KO mice displayed elevated DA synthesis and release, hyperlocomotion and supersensitivity to the psychomotor effects of cocaine. The mice also exhibited increased place preference for cocaine and enhanced motivation for food reward. Our results highlight the importance of D 2 autoreceptors in the regulation of DA neurotransmission and demonstrate that D2 autoreceptors are important for normal motor function, food-seeking behavior, and sensitivity to the locomotor and rewarding properties of cocaine. © 2011 Nature America, Inc. All rights reserved.
author	Bello Gay, Estefanía Pilar Gelman, Diego Matías Noaín, Daniela María Clara Rubinstein, Marcelo
author_facet	Bello Gay, Estefanía Pilar Gelman, Diego Matías Noaín, Daniela María Clara Rubinstein, Marcelo
author_sort	Bello Gay, Estefanía Pilar
title	Cocaine supersensitivity and enhanced motivation for reward in mice lacking dopamine D2 autoreceptors
title_short	Cocaine supersensitivity and enhanced motivation for reward in mice lacking dopamine D2 autoreceptors
title_full	Cocaine supersensitivity and enhanced motivation for reward in mice lacking dopamine D2 autoreceptors
title_fullStr	Cocaine supersensitivity and enhanced motivation for reward in mice lacking dopamine D2 autoreceptors
title_full_unstemmed	Cocaine supersensitivity and enhanced motivation for reward in mice lacking dopamine D2 autoreceptors
title_sort	cocaine supersensitivity and enhanced motivation for reward in mice lacking dopamine d2 autoreceptors
publishDate	2011
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10976256_v14_n8_p1033_Bello http://hdl.handle.net/20.500.12110/paper_10976256_v14_n8_p1033_Bello
work_keys_str_mv	AT bellogayestefaniapilar cocainesupersensitivityandenhancedmotivationforrewardinmicelackingdopamined2autoreceptors AT gelmandiegomatias cocainesupersensitivityandenhancedmotivationforrewardinmicelackingdopamined2autoreceptors AT noaindanielamariaclara cocainesupersensitivityandenhancedmotivationforrewardinmicelackingdopamined2autoreceptors AT rubinsteinmarcelo cocainesupersensitivityandenhancedmotivationforrewardinmicelackingdopamined2autoreceptors
_version_	1840325824548438016

Cocaine supersensitivity and enhanced motivation for reward in mice lacking dopamine D2 autoreceptors

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