Brain stimulation and morphine reward deficits in dopamine D2 receptor-deficient mice

Rationale: The rewarding effects of lateral hypothalamic brain stimulation, various natural rewards, and several drugs of abuse are attenuated by D1 or D2 dopamine receptor (D1R or D2R) antagonists. Much of the evidence for dopaminergic involvement in rewards is based on pharmacological agents with...

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Autores: Elmer, G. I., Pieper, J. O., Levy, J., Rubinstein, Marcelo, Low, Malcolm J., Grandy, David K., Wise, R.A.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2005
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/79901
Acceso en línea:http://hdl.handle.net/11336/79901
Access Level:acceso abierto
Palabra clave:Addiction
Amphetamine
Depolarization
Icss
Knockout
Mice
Neuroleptic
Opioid
Reinforcement
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
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network_acronym_str AR
network_name_str Argentina
repository_id_str
spelling Brain stimulation and morphine reward deficits in dopamine D2 receptor-deficient miceElmer, G. I.Pieper, J. O.Levy, J.Rubinstein, MarceloLow, Malcolm J.Grandy, David K.Wise, R.A.AddictionAmphetamineDepolarizationIcssKnockoutMiceNeurolepticOpioidReinforcementhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Rationale: The rewarding effects of lateral hypothalamic brain stimulation, various natural rewards, and several drugs of abuse are attenuated by D1 or D2 dopamine receptor (D1R or D2R) antagonists. Much of the evidence for dopaminergic involvement in rewards is based on pharmacological agents with limited or "relative" selectivity for dopamine receptor subtypes. Genetically engineered animal models provide a complementary approach to pharmacological investigations. Objectives: In the present study, we explored the contribution of dopamine D2Rs to (1) brain stimulation reward (BSR) and (2) the potentiation of this behavior by morphine and amphetamine using D2R-deficient mice. Methods: Wild-type (D2Rwt), heterozygous (D2Rhet), and D2R knockout (D2Rko) mice were trained to turn a wheel for rewarding brain stimulation. Once equivalent rate-frequency curves were established, morphine-induced (0, 1.0, 3.0, and 5.6 mg/kg s.c.) and amphetamine-induced (0, 1.0, 2.0, and 4.0 mg/kg i.p.) potentiations of BSR were determined. Results: The D2Rko mice required approximately 50% more stimulation than the D2Rwt mice did. With the equi-rewarding levels of stimulation current, amphetamine potentiated BSR equally across the three genotypes. In contrast, morphine potentiated rewarding stimulation in the D2Rwt, had no effect in the D2Rhet, and antagonized rewarding stimulation in the D2Rko mice. Conclusions: D2R elimination decreases, but does not eliminate, the rewarding effects of lateral hypothalamic stimulation. After compensation for this deficit, amphetamine continues to potentiate BSR, while morphine does not.Fil: Elmer, G. I.. University of Maryland; Estados UnidosFil: Pieper, J. O.. Behavioral Neuroscienc; Estados UnidosFil: Levy, J.. Behavioral Neuroscienc; Estados UnidosFil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Low, Malcolm J.. Oregon Health and Science University; Estados UnidosFil: Grandy, David K.. Oregon Health and Science University; Estados UnidosFil: Wise, R.A.. Behavioral Neuroscienc; Estados UnidosSpringer2005-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/79901Elmer, G. I.; Pieper, J. O.; Levy, J.; Rubinstein, Marcelo; Low, Malcolm J.; et al.; Brain stimulation and morphine reward deficits in dopamine D2 receptor-deficient mice; Springer; Psychopharmacology; 182; 1; 10-2005; 33-440033-3158CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pubmed/16136297info:eu-repo/semantics/altIdentifier/doi/10.1007/s00213-005-0051-2info:eu-repo/semantics/altIdentifier/url/link.springer.com/article/10.1007/s00213-005-0051-2info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2024-05-08T14:29:08Zoai:ri.conicet.gov.ar:11336/79901instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982024-05-08 14:29:08.611CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Brain stimulation and morphine reward deficits in dopamine D2 receptor-deficient mice
title Brain stimulation and morphine reward deficits in dopamine D2 receptor-deficient mice
spellingShingle Brain stimulation and morphine reward deficits in dopamine D2 receptor-deficient mice
Elmer, G. I.
Addiction
Amphetamine
Depolarization
Icss
Knockout
Mice
Neuroleptic
Opioid
Reinforcement
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
title_short Brain stimulation and morphine reward deficits in dopamine D2 receptor-deficient mice
title_full Brain stimulation and morphine reward deficits in dopamine D2 receptor-deficient mice
title_fullStr Brain stimulation and morphine reward deficits in dopamine D2 receptor-deficient mice
title_full_unstemmed Brain stimulation and morphine reward deficits in dopamine D2 receptor-deficient mice
title_sort Brain stimulation and morphine reward deficits in dopamine D2 receptor-deficient mice
dc.creator.none.fl_str_mv Elmer, G. I.
Pieper, J. O.
Levy, J.
Rubinstein, Marcelo
Low, Malcolm J.
Grandy, David K.
Wise, R.A.
author Elmer, G. I.
author_facet Elmer, G. I.
Pieper, J. O.
Levy, J.
Rubinstein, Marcelo
Low, Malcolm J.
Grandy, David K.
Wise, R.A.
author_role author
author2 Pieper, J. O.
Levy, J.
Rubinstein, Marcelo
Low, Malcolm J.
Grandy, David K.
Wise, R.A.
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Addiction
Amphetamine
Depolarization
Icss
Knockout
Mice
Neuroleptic
Opioid
Reinforcement
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
topic Addiction
Amphetamine
Depolarization
Icss
Knockout
Mice
Neuroleptic
Opioid
Reinforcement
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
description Rationale: The rewarding effects of lateral hypothalamic brain stimulation, various natural rewards, and several drugs of abuse are attenuated by D1 or D2 dopamine receptor (D1R or D2R) antagonists. Much of the evidence for dopaminergic involvement in rewards is based on pharmacological agents with limited or "relative" selectivity for dopamine receptor subtypes. Genetically engineered animal models provide a complementary approach to pharmacological investigations. Objectives: In the present study, we explored the contribution of dopamine D2Rs to (1) brain stimulation reward (BSR) and (2) the potentiation of this behavior by morphine and amphetamine using D2R-deficient mice. Methods: Wild-type (D2Rwt), heterozygous (D2Rhet), and D2R knockout (D2Rko) mice were trained to turn a wheel for rewarding brain stimulation. Once equivalent rate-frequency curves were established, morphine-induced (0, 1.0, 3.0, and 5.6 mg/kg s.c.) and amphetamine-induced (0, 1.0, 2.0, and 4.0 mg/kg i.p.) potentiations of BSR were determined. Results: The D2Rko mice required approximately 50% more stimulation than the D2Rwt mice did. With the equi-rewarding levels of stimulation current, amphetamine potentiated BSR equally across the three genotypes. In contrast, morphine potentiated rewarding stimulation in the D2Rwt, had no effect in the D2Rhet, and antagonized rewarding stimulation in the D2Rko mice. Conclusions: D2R elimination decreases, but does not eliminate, the rewarding effects of lateral hypothalamic stimulation. After compensation for this deficit, amphetamine continues to potentiate BSR, while morphine does not.
publishDate 2005
dc.date.none.fl_str_mv 2005-10
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/79901
Elmer, G. I.; Pieper, J. O.; Levy, J.; Rubinstein, Marcelo; Low, Malcolm J.; et al.; Brain stimulation and morphine reward deficits in dopamine D2 receptor-deficient mice; Springer; Psychopharmacology; 182; 1; 10-2005; 33-44
0033-3158
CONICET Digital
CONICET
url http://hdl.handle.net/11336/79901
identifier_str_mv Elmer, G. I.; Pieper, J. O.; Levy, J.; Rubinstein, Marcelo; Low, Malcolm J.; et al.; Brain stimulation and morphine reward deficits in dopamine D2 receptor-deficient mice; Springer; Psychopharmacology; 182; 1; 10-2005; 33-44
0033-3158
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pubmed/16136297
info:eu-repo/semantics/altIdentifier/doi/10.1007/s00213-005-0051-2
info:eu-repo/semantics/altIdentifier/url/link.springer.com/article/10.1007/s00213-005-0051-2
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 15,811543

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