Cocaine-induced locomotor activity and cocaine discrimination in dopamine D2 receptor mutant mice

Rationale: Dopamine (DA) D2-like antagonists block several effects of cocaine, including its locomotor stimulant and interoceptive discriminative-stimulus effects. Because these compounds generally lack selectivity among the D2-like DA receptors, the specific roles of the subtypes remain unclear. Ob...

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Detalles Bibliográficos
Autores: Chausmer, Allison L., Elmer, Gregory I., Rubinstein, Marcelo, Low, Malcolm J., Grandy, David K., Katz, Jonathan L.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2002
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/79709
Acceso en línea:http://hdl.handle.net/11336/79709
Access Level:acceso abierto
Palabra clave:Cocaine
D2
Dopamine
Drug Discrimination
Knockout
Locomotor Activity
Raclopride
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
dc.title.none.fl_str_mv Cocaine-induced locomotor activity and cocaine discrimination in dopamine D2 receptor mutant mice
title Cocaine-induced locomotor activity and cocaine discrimination in dopamine D2 receptor mutant mice
spellingShingle Cocaine-induced locomotor activity and cocaine discrimination in dopamine D2 receptor mutant mice
Chausmer, Allison L.
Cocaine
D2
Dopamine
Drug Discrimination
Knockout
Locomotor Activity
Raclopride
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
title_short Cocaine-induced locomotor activity and cocaine discrimination in dopamine D2 receptor mutant mice
title_full Cocaine-induced locomotor activity and cocaine discrimination in dopamine D2 receptor mutant mice
title_fullStr Cocaine-induced locomotor activity and cocaine discrimination in dopamine D2 receptor mutant mice
title_full_unstemmed Cocaine-induced locomotor activity and cocaine discrimination in dopamine D2 receptor mutant mice
title_sort Cocaine-induced locomotor activity and cocaine discrimination in dopamine D2 receptor mutant mice
dc.creator.none.fl_str_mv Chausmer, Allison L.
Elmer, Gregory I.
Rubinstein, Marcelo
Low, Malcolm J.
Grandy, David K.
Katz, Jonathan L.
author Chausmer, Allison L.
author_facet Chausmer, Allison L.
Elmer, Gregory I.
Rubinstein, Marcelo
Low, Malcolm J.
Grandy, David K.
Katz, Jonathan L.
author_role author
author2 Elmer, Gregory I.
Rubinstein, Marcelo
Low, Malcolm J.
Grandy, David K.
Katz, Jonathan L.
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Cocaine
D2
Dopamine
Drug Discrimination
Knockout
Locomotor Activity
Raclopride
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
topic Cocaine
D2
Dopamine
Drug Discrimination
Knockout
Locomotor Activity
Raclopride
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
description Rationale: Dopamine (DA) D2-like antagonists block several effects of cocaine, including its locomotor stimulant and interoceptive discriminative-stimulus effects. Because these compounds generally lack selectivity among the D2-like DA receptors, the specific roles of the subtypes remain unclear. Objectives: DA D2 receptor knockout (DA D2R KO), heterozygous (HET), and wild-type (WT) mice were used to study the role of D2 DA receptors in the effects of cocaine. Some effects of the relatively selective DA D2-like antagonist raclopride were also studied to further assess the role of D2 receptors. Methods: DA D2R KO, HET, and WT mice were treated with cocaine (1-10 mg/kg) or vehicle, and their horizontal locomotor activity was assessed. The mice were also trained to discriminate i.p. injections of saline from cocaine (10 mg/kg) using a two-response key, fixed-ratio-20 response, food-reinforcement procedure. A range of doses of cocaine (1.0-17 mg/kg) was administered before 15-min test sessions. Results: Both DA D2R KO and HET mice showed reduced levels of horizontal activity relative to WT mice. Cocaine dose dependently stimulated activity in each genotype, with the highest level of activity induced in the DA D2R WT mice. All three genotypes acquired the discrimination of 10 mg/kg cocaine; tested doses of 1.0-10.0 mg/kg produced dose-related increases in the number of cocaine-appropriate responses. Raclopride, at inactive to fully active doses (0.1-1.0 mg/kg), did not fully substitute for cocaine. Raclopride dose dependently shifted the cocaine dose-effect curve to the right in DA D2R WT and HET mice. However, in DA D2R KO mice, raclopride was inactive as an antagonist. Conclusions: The present data indicate an involvement of D2 DA receptors in the locomotor-stimulating effects and the interoceptive discriminative-stimulus effects of cocaine in WT subjects. However, the D2 receptor is not necessary for the effects, suggesting redundant dopaminergic mechanisms for the discriminative-stimulus interoceptive effects of cocaine.
publishDate 2002
dc.date.none.fl_str_mv 2002-08
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/11336/79709
Chausmer, Allison L.; Elmer, Gregory I.; Rubinstein, Marcelo; Low, Malcolm J.; Grandy, David K.; et al.; Cocaine-induced locomotor activity and cocaine discrimination in dopamine D2 receptor mutant mice; Springer; Psychopharmacology; 163; 1; 8-2002; 54-61
0033-3158
CONICET Digital
CONICET
url http://hdl.handle.net/11336/79709
identifier_str_mv Chausmer, Allison L.; Elmer, Gregory I.; Rubinstein, Marcelo; Low, Malcolm J.; Grandy, David K.; et al.; Cocaine-induced locomotor activity and cocaine discrimination in dopamine D2 receptor mutant mice; Springer; Psychopharmacology; 163; 1; 8-2002; 54-61
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/doi/10.1007/s00213-002-1142-y
info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007/s00213-002-1142-y
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pubmed/12185400
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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spelling Cocaine-induced locomotor activity and cocaine discrimination in dopamine D2 receptor mutant miceChausmer, Allison L.Elmer, Gregory I.Rubinstein, MarceloLow, Malcolm J.Grandy, David K.Katz, Jonathan L.CocaineD2DopamineDrug DiscriminationKnockoutLocomotor ActivityRaclopridehttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Rationale: Dopamine (DA) D2-like antagonists block several effects of cocaine, including its locomotor stimulant and interoceptive discriminative-stimulus effects. Because these compounds generally lack selectivity among the D2-like DA receptors, the specific roles of the subtypes remain unclear. Objectives: DA D2 receptor knockout (DA D2R KO), heterozygous (HET), and wild-type (WT) mice were used to study the role of D2 DA receptors in the effects of cocaine. Some effects of the relatively selective DA D2-like antagonist raclopride were also studied to further assess the role of D2 receptors. Methods: DA D2R KO, HET, and WT mice were treated with cocaine (1-10 mg/kg) or vehicle, and their horizontal locomotor activity was assessed. The mice were also trained to discriminate i.p. injections of saline from cocaine (10 mg/kg) using a two-response key, fixed-ratio-20 response, food-reinforcement procedure. A range of doses of cocaine (1.0-17 mg/kg) was administered before 15-min test sessions. Results: Both DA D2R KO and HET mice showed reduced levels of horizontal activity relative to WT mice. Cocaine dose dependently stimulated activity in each genotype, with the highest level of activity induced in the DA D2R WT mice. All three genotypes acquired the discrimination of 10 mg/kg cocaine; tested doses of 1.0-10.0 mg/kg produced dose-related increases in the number of cocaine-appropriate responses. Raclopride, at inactive to fully active doses (0.1-1.0 mg/kg), did not fully substitute for cocaine. Raclopride dose dependently shifted the cocaine dose-effect curve to the right in DA D2R WT and HET mice. However, in DA D2R KO mice, raclopride was inactive as an antagonist. Conclusions: The present data indicate an involvement of D2 DA receptors in the locomotor-stimulating effects and the interoceptive discriminative-stimulus effects of cocaine in WT subjects. However, the D2 receptor is not necessary for the effects, suggesting redundant dopaminergic mechanisms for the discriminative-stimulus interoceptive effects of cocaine.Fil: Chausmer, Allison L.. National Institutes of Health; Estados UnidosFil: Elmer, Gregory I.. University of Maryland School of Medicine; Estados UnidosFil: Rubinstein, Marcelo. Oregon Health and Science University; Estados Unidos. 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: Katz, Jonathan L.. National Institutes of Health; Estados UnidosSpringer2002-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/79709Chausmer, Allison L.; Elmer, Gregory I.; Rubinstein, Marcelo; Low, Malcolm J.; Grandy, David K.; et al.; Cocaine-induced locomotor activity and cocaine discrimination in dopamine D2 receptor mutant mice; Springer; Psychopharmacology; 163; 1; 8-2002; 54-610033-3158CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1007/s00213-002-1142-yinfo:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007/s00213-002-1142-yinfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pubmed/12185400info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2024-05-08T14:10:23Zoai:ri.conicet.gov.ar:11336/79709instacron: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 14:10:24.146CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
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