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The Dopamine Uptake Inhibitor 3α-[bis(4′-fluorophenyl)metoxy]-tropane Reduces Cocaine-Induced Early-Gene Expression, Locomotor Activity, and Conditioned Reward
dc.contributor.author | Velázquez Sánchez, Clara | |
dc.contributor.author | Ferragud, Antonio | |
dc.contributor.author | Hernández-Rabaza, Vicente | |
dc.contributor.author | Nácher, Amparo | |
dc.contributor.author | Merino, Virginia | |
dc.contributor.author | Carda, Miguel | |
dc.contributor.author | Murga, Juan | |
dc.contributor.author | Canales, Juan José | |
dc.date.accessioned | 2014-06-30T10:07:03Z | |
dc.date.available | 2014-06-30T10:07:03Z | |
dc.date.issued | 2009 | |
dc.identifier.issn | 0893-133X | |
dc.identifier.uri | http://hdl.handle.net/10234/96533 | |
dc.description.abstract | Benztropine (BZT) analogs, a family of high-affinity dopamine transporter ligands, are molecules that exhibit pharmacological and behavioral characteristics predictive of significant therapeutic potential in cocaine addiction. Here, we examined in mice the effects of 3α-[bis(4′-fluorophenyl)metoxy]-tropane (AHN-1055) on motor activity, conditioned place preference (CPP) and c-Fos expression in the striatum. AHN-1055 produced mild attenuation of spontaneous locomotor activity at a low dose (1 mg/kg) and weak stimulation at a higher dose (10 mg/kg). In parallel, the BZT analog significantly increased c-Fos expression in the dorsolateral caudoputamen at the high dose, whereas producing marginal decreases at low and moderate doses (1, 3 mg/kg) in both dorsal and ventral striatum. Interaction assays showed that cocaine's ability to stimulate locomotor activity was decreased by AHN-1055 treatment, but not by treatment with D-amphetamine. Such reduced ability did not result from an increase in stereotyped behavior. Another dopamine uptake inhibitor, nomifensine, decreased cocaine-induced locomotor activity but evoked by itself intense motor stereotypies. Remarkably, the BZT analog dose-dependently blocked cocaine-induced CPP without producing CPP when given alone, and blocked in conditioned mice cocaine-stimulated early-gene activation in the nucleus accumbens and dorsomedial striatum. These observations provide evidence that AHN-1055 does not behave as a classical psychomotor stimulant and that some of its properties, including attenuation of cocaine-induced striatal c-Fos expression, locomotor stimulation, and CPP, support its candidacy, and that of structurally related molecules, as possible pharmacotherapies in cocaine addiction. | ca_CA |
dc.format.extent | 10 p. | ca_CA |
dc.format.mimetype | application/pdf | ca_CA |
dc.language.iso | eng | ca_CA |
dc.publisher | Nature Publishing Group | ca_CA |
dc.relation.isPartOf | Neuropsychopharmacology, 34, p. 2497–2507 | ca_CA |
dc.rights | Copyright 2009 Nature Publishing Group | ca_CA |
dc.rights.uri | http://rightsstatements.org/vocab/InC/1.0/ | * |
dc.subject | cocaine | ca_CA |
dc.subject | BZT derivative | ca_CA |
dc.subject | AHN-1055 | ca_CA |
dc.subject | locomotor activity | ca_CA |
dc.subject | place preference | ca_CA |
dc.subject | c-Fos | ca_CA |
dc.title | The Dopamine Uptake Inhibitor 3α-[bis(4′-fluorophenyl)metoxy]-tropane Reduces Cocaine-Induced Early-Gene Expression, Locomotor Activity, and Conditioned Reward | ca_CA |
dc.type | info:eu-repo/semantics/article | ca_CA |
dc.identifier.doi | http://dx.doi.org/10.1038/npp.2009.78 | |
dc.rights.accessRights | info:eu-repo/semantics/restrictedAccess | ca_CA |
dc.relation.publisherVersion | http://www.nature.com/npp/journal/v34/n12/abs/npp200978a.html | ca_CA |
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