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dc.contributor.author
Chausmer, Allison L.
dc.contributor.author
Elmer, Gregory I.
dc.contributor.author
Rubinstein, Marcelo
dc.contributor.author
Low, Malcolm J.
dc.contributor.author
Grandy, David K.
dc.contributor.author
Katz, Jonathan L.
dc.date.available
2019-07-16T20:54:34Z
dc.date.issued
2002-08
dc.identifier.citation
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
dc.identifier.issn
0033-3158
dc.identifier.uri
http://hdl.handle.net/11336/79709
dc.description.abstract
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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Springer
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Cocaine
dc.subject
D2
dc.subject
Dopamine
dc.subject
Drug Discrimination
dc.subject
Knockout
dc.subject
Locomotor Activity
dc.subject
Raclopride
dc.subject.classification
Neurociencias
dc.subject.classification
Medicina Básica
dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Cocaine-induced locomotor activity and cocaine discrimination in dopamine D2 receptor mutant mice
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2019-07-16T14:13:03Z
dc.journal.volume
163
dc.journal.number
1
dc.journal.pagination
54-61
dc.journal.pais
Alemania
dc.journal.ciudad
Berlin
dc.description.fil
Fil: Chausmer, Allison L.. National Institutes of Health; Estados Unidos
dc.description.fil
Fil: Elmer, Gregory I.. University of Maryland School of Medicine; Estados Unidos
dc.description.fil
Fil: 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"; Argentina
dc.description.fil
Fil: Low, Malcolm J.. Oregon Health and Science University; Estados Unidos
dc.description.fil
Fil: Grandy, David K.. Oregon Health and Science University; Estados Unidos
dc.description.fil
Fil: Katz, Jonathan L.. National Institutes of Health; Estados Unidos
dc.journal.title
Psychopharmacology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1007/s00213-002-1142-y
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007/s00213-002-1142-y
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pubmed/12185400


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