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

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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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Autor principal: Bello, E.P
Otros Autores: Mateo, Y., Gelman, D.M, Noaín, D., Shin, J.H, Low, M.J, Alvarez, V.A, Lovinger, D.M, Rubinstein, M.
Formato: Capítulo de libro
Lenguaje:Inglés
Publicado: 2011
Acceso en línea:Registro en Scopus
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Biblioteca Central Dr. Luis F. Leloir (FCEN) de Universidad de Buenos Aires
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024 7 |2 cas  |a cocaine, 50-36-2, 53-21-4, 5937-29-1; 3-hydroxybenzylhydrazine, 637-33-2; Baclofen, 1134-47-0; Cocaine, 50-36-2; Dihydroxyphenylalanine, 63-84-3; Dopamine Agonists; Dopamine Antagonists; Dopamine Uptake Inhibitors; Enzyme Inhibitors; GABA-B Receptor Agonists; Hydrazines; Quinpirole, 85760-74-3; Receptors, Dopamine D2; Sulpiride, 15676-16-1 
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100 1 |a Bello, E.P. 
245 1 0 |a Cocaine supersensitivity and enhanced motivation for reward in mice lacking dopamine D2 autoreceptors 
260 |c 2011 
270 1 0 |m Rubinstein, M.; Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina; email: mrubins@dna.uba.ar 
506 |2 openaire  |e Política editorial 
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520 3 |a 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.  |l eng 
536 |a Detalles de la financiación: Consejo Nacional de Investigaciones Científicas y Técnicas 
536 |a Detalles de la financiación: Foundation for the National Institutes of Health, R01-MH61326 
536 |a Detalles de la financiación: National Science Foundation, INT-9901278 
536 |a Detalles de la financiación: Agencia Nacional de Promoción Científica y Tecnológica 
536 |a Detalles de la financiación: Howard Hughes Medical Institute 
536 |a Detalles de la financiación: Universidad de Buenos Aires 
536 |a Detalles de la financiación: Consejo Nacional de Investigaciones Científicas y Técnicas 
536 |a Detalles de la financiación: National Institute of Neurological Disorders and Stroke 
536 |a Detalles de la financiación: 1Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina. 2Section on Synaptic Pharmacology, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, US National Institutes of Health, Bethesda, Maryland, USA. 3Section on Neuronal Structure, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, US National Institutes of Health, Bethesda, Maryland, USA. 4Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA. 5Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina. 6These authors contributed equally to this work. Correspondence should be addressed to M.R. (mrubins@dna.uba.ar). 
536 |a Detalles de la financiación: We thank J. Sztein, G. Levin, C. Bäckman, V. Rodríguez, R. Lorenzo, S. Nemirovsky, M. Peper, S. Merani, C. Carbone, F. Maschi and M. Baetscher for their scientific and technical assistance. This work was supported in part by an International Research Scholar Grant of the Howard Hughes Medical Institute (M.R.), Universidad de Buenos Aires (M.R.) and Agencia Nacional de Promoción Científica y Tecnológica (M.R.), National Science Foundation grant INT-9901278 (M.J.L. and M.R.) and US National Institutes of Health grant R01-MH61326 (M.J.L.). E.P.B., D.N. and D.M.G. received doctoral fellowships from the Consejo Nacional de Investigaciones Científicas y Técnicas, Argentina. Y.M., J.H.S., V.A.A. and D.M.L. were supported by the Division of Intramural Clinical and Biological Research of the National Institute on Alcohol Abuse and Alcoholism. J.H.S. and V.A.A. received support from the Intramural Program of the National Institute of Neurological Disorders and Stroke. 
593 |a Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina 
593 |a Section on Synaptic Pharmacology, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, United States 
593 |a Section on Neuronal Structure, Laboratory for Integrative Neuroscience, US National Institutes of Health, Bethesda, MD, United States 
593 |a Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, United States 
593 |a Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina 
690 1 0 |a COCAINE 
690 1 0 |a DOPAMINE 2 RECEPTOR 
690 1 0 |a DOPAMINE AUTORECEPTOR 
690 1 0 |a ARTICLE 
690 1 0 |a DOPAMINERGIC NERVE CELL 
690 1 0 |a FEEDING BEHAVIOR 
690 1 0 |a MOTIVATION 
690 1 0 |a MOTOR PERFORMANCE 
690 1 0 |a NERVE CELL INHIBITION 
690 1 0 |a NEUROTRANSMISSION 
690 1 0 |a PRIORITY JOURNAL 
690 1 0 |a PSYCHOMOTOR ACTIVITY 
690 1 0 |a SUPERSENSITIVITY 
690 1 0 |a SYNAPSE 
690 1 0 |a ANALYSIS OF VARIANCE 
690 1 0 |a ANIMALS 
690 1 0 |a AUTORADIOGRAPHY 
690 1 0 |a BACLOFEN 
690 1 0 |a CHOICE BEHAVIOR 
690 1 0 |a COCAINE 
690 1 0 |a CONDITIONING, OPERANT 
690 1 0 |a DIHYDROXYPHENYLALANINE 
690 1 0 |a DOPAMINE 
690 1 0 |a DOPAMINE AGONISTS 
690 1 0 |a DOPAMINE ANTAGONISTS 
690 1 0 |a DOPAMINE UPTAKE INHIBITORS 
690 1 0 |a DRUG INTERACTIONS 
690 1 0 |a ENZYME INHIBITORS 
690 1 0 |a EXPLORATORY BEHAVIOR 
690 1 0 |a FOOD 
690 1 0 |a GABA-B RECEPTOR AGONISTS 
690 1 0 |a HYDRAZINES 
690 1 0 |a HYPERKINESIS 
690 1 0 |a MAZE LEARNING 
690 1 0 |a MEMBRANE POTENTIALS 
690 1 0 |a MESENCEPHALON 
690 1 0 |a MICE 
690 1 0 |a MICE, KNOCKOUT 
690 1 0 |a MOTIVATION 
690 1 0 |a MOTOR ACTIVITY 
690 1 0 |a NEURONS 
690 1 0 |a QUINPIROLE 
690 1 0 |a RECEPTORS, DOPAMINE D2 
690 1 0 |a REINFORCEMENT SCHEDULE 
690 1 0 |a REWARD 
690 1 0 |a SULPIRIDE 
700 1 |a Mateo, Y. 
700 1 |a Gelman, D.M. 
700 1 |a Noaín, D. 
700 1 |a Shin, J.H. 
700 1 |a Low, M.J. 
700 1 |a Alvarez, V.A. 
700 1 |a Lovinger, D.M. 
700 1 |a Rubinstein, M. 
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856 4 0 |u https://hdl.handle.net/20.500.12110/paper_10976256_v14_n8_p1033_Bello  |y Handle 
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