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dc.contributor.authorSanterre, Jessica L.
dc.contributor.authorNunes, Eric J.
dc.contributor.authorKovner, Rotem
dc.contributor.authorLeser, Chelsea E.
dc.contributor.authorRandall, Patrick A.
dc.contributor.authorCollins, Lyndsey E.
dc.contributor.authorLópez Cruz, Laura
dc.contributor.authorCorrea, Merce
dc.contributor.authorBaqi, Younis
dc.contributor.authorMüller, Christa E.
dc.contributor.authorSalamone, John
dc.date.accessioned2013-06-26T14:29:41Z
dc.date.available2013-06-26T14:29:41Z
dc.date.issued2012
dc.identifier.issn1873-5177
dc.identifier.issn0091-3057
dc.identifier.urihttp://hdl.handle.net/10234/68460
dc.description.abstractAdenosine A2A and dopamine D2 receptors interact to regulate diverse aspects of ventral and dorsal striatal functions related to motivational and motor processes, and it has been suggested that adenosine A2A antagonists could be useful for the treatment of depression, parkinsonism and other disorders. The present experiments were performed to characterize the effects of MSX-4, which is an amino acid ester prodrug of the potent and selective adenosine A2A receptor antagonist MSX-2, by assessing its ability to reverse pharmacologically induced motivational and motor impairments. In the first group of studies, MSX-4 reversed the effects of the D2 antagonist eticlopride on a concurrent lever pressing/chow feeding task that is used as a measure of effort-related choice behavior. MSX-4 was less potent after intraperitoneal administration than the comparison compound, MSX-3, though both were equally efficacious. With this task, MSX-4 was orally active in the same dose range as MSX-3. MSX-4 also reversed the locomotor suppression induced by eticlopride in the open field, but did not induce anxiogenic effects as measured by the relative amount of interior activity. Behaviorally active doses of MSX-4 also attenuated the increase in c-Fos and pDARPP-32(Thr34) expression in nucleus accumbens core that was induced by injections of eticlopride. In addition, MSX-4 suppressed the oral tremor induced by the anticholinesterase galantamine, which is consistent with an antiparkinsonian profile. These actions of MSX-4 indicate that this compound could have potential utility as a treatment for parkinsonism, as well as some of the motivational symptoms of depression and other disorders.ca_CA
dc.format.extent11 p.ca_CA
dc.language.isoengca_CA
dc.publisherElsevierca_CA
dc.relation.isPartOfPharmacology Biochemistry and Behavior Volume 102, Issue 4, October 2012ca_CA
dc.rights© 2012 Elsevier Inc. All rights reserved.ca_CA
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/*
dc.subjectDepressionca_CA
dc.subjectEffort-related choice behaviorca_CA
dc.subjectParkinson's diseaseca_CA
dc.subjectDrug-induced parkinsonismca_CA
dc.subjectLocomotionca_CA
dc.subjectTremulous jaw movementsca_CA
dc.subjectc-Fosca_CA
dc.subjectDARPP-32ca_CA
dc.titleThe novel adenosine A2A antagonist prodrug MSX-4 is effective in animal models related to motivational and motor functionsca_CA
dc.typeinfo:eu-repo/semantics/articleca_CA
dc.identifier.doihttp://dx.doi.org/:10.1016/j.pbb.2012.06.009
dc.rights.accessRightsinfo:eu-repo/semantics/restrictedAccessca_CA
dc.relation.publisherVersionhttp://ac.els-cdn.com/S0091305712001645/1-s2.0-S0091305712001645-main.pdf?_tid=c21cc852-de6b-11e2-b7d0-00000aab0f01&acdnat=1372256697_6d4c1d784fe67d3681ebef70451f3448ca_CA
dc.type.versioninfo:eu-repo/semantics/publishedVersionca_CA


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