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dc.contributor.author
Zahniser, Nancy R.
dc.contributor.author
Simosky, Johanna K.
dc.contributor.author
Mayfield, R. Dayne
dc.contributor.author
Negri, Cori A.
dc.contributor.author
Hanania, Taleen
dc.contributor.author
Larson, Gaynor A.
dc.contributor.author
Kelly, Michele A.
dc.contributor.author
Grandy, David K.
dc.contributor.author
Rubinstein, Marcelo
dc.contributor.author
Low, Malcolm J.
dc.contributor.author
Fredholm, Bertil B.
dc.date.available
2019-03-18T16:08:32Z
dc.date.issued
2000-08
dc.identifier.citation
Zahniser, Nancy R.; Simosky, Johanna K.; Mayfield, R. Dayne; Negri, Cori A.; Hanania, Taleen; et al.; Functional Uncoupling of Adenosine A 2A Receptors and Reduced Response to Caffeine in Mice Lacking Dopamine D 2 Receptors; Society for Neuroscience; Journal of Neuroscience; 20; 16; 8-2000; 5949-5957
dc.identifier.issn
0270-6474
dc.identifier.uri
http://hdl.handle.net/11336/71855
dc.description.abstract
Dopamine D(2) receptors (Rs) and adenosine A(2A)Rs are coexpressed on striatopallidal neurons, where they mediate opposing actions. In agreement with the idea that D(2)Rs tonically inhibit GABA release from these neurons, stimulation-evoked GABA release was significantly greater from striatal/pallidal slices from D(2)R null mutant (D(2)R(-/-)) than from wild-type (D(2)R(+/+)) mice. Release from heterozygous (D(2)R(+/-)) slices was intermediate. However, contrary to predictions that A(2A)R effects would be enhanced in D(2)R-deficient mice, the A(2A)R agonist CGS 21680 significantly increased GABA release only from D(2)R(+/+) slices. CGS 21680 modulation was observed when D(2)Rs were antagonized by raclopride, suggesting that an acute absence of D(2)Rs cannot explain the results. The lack of CGS 21680 modulation in the D(2)R-deficient mice was also not caused by a compensatory downregulation of A(2A)Rs in the striatum or globus pallidus. However, CGS 21680 significantly stimulated cAMP production only in D(2)R(+/+) striatal/pallidal slices. This functional uncoupling of A(2A)Rs in the D(2)R-deficient mice was not explained by reduced expression of G(s), G(olf), or type VI adenylyl cyclase. Locomotor activity induced by the adenosine receptor antagonist caffeine was significantly less pronounced in D(2)R(-/-) mice than in D(2)R(+/+) and D(2)R(+/-) mice, further supporting the idea that D(2)Rs are required for caffeine activation. Caffeine increased c-fos only in D(2)R(-/-) globus pallidus. The present results show that a targeted disruption of the D(2)R reduces coupling of A(2A)Rs on striatopallidal neurons and thereby responses to drugs that act on adenosine receptors. They also reinforce the ideas that D(2)Rs and A(2A)Rs are functionally opposed and that D(2)R-mediated effects normally predominate.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Society for Neuroscience
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by/2.5/ar/
dc.subject
Dopamina
dc.subject
Adenosina
dc.subject
Mrna
dc.subject
Cafeína
dc.subject
Actividad Locomotora
dc.subject.classification
Inmunología
dc.subject.classification
Medicina Básica
dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Functional Uncoupling of Adenosine A 2A Receptors and Reduced Response to Caffeine in Mice Lacking Dopamine D 2 Receptors
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2019-03-14T14:10:54Z
dc.journal.volume
20
dc.journal.number
16
dc.journal.pagination
5949-5957
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Washington DC
dc.description.fil
Fil: Zahniser, Nancy R.. University of Colorado; Estados Unidos
dc.description.fil
Fil: Simosky, Johanna K.. University of Colorado; Estados Unidos
dc.description.fil
Fil: Mayfield, R. Dayne. University of Colorado; Estados Unidos
dc.description.fil
Fil: Negri, Cori A.. University of Colorado; Estados Unidos
dc.description.fil
Fil: Hanania, Taleen. University of Colorado; Estados Unidos
dc.description.fil
Fil: Larson, Gaynor A.. University of Colorado; Estados Unidos
dc.description.fil
Fil: Kelly, Michele A.. University of Oregon; Estados Unidos
dc.description.fil
Fil: Grandy, David K.. University of Oregon; Estados Unidos
dc.description.fil
Fil: Rubinstein, Marcelo. 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.. University of Oregon; Estados Unidos
dc.description.fil
Fil: Fredholm, Bertil B.. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia
dc.journal.title
Journal of Neuroscience
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://doi.org/10.1523/JNEUROSCI.20-16-05949.2000
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.jneurosci.org/content/20/16/5949
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