Mostrar el registro sencillo del ítem
The Novel Atypical Dopamine Uptake Inhibitor (S)-CE-123 Partially Reverses the Effort-Related Effects of the Dopamine Depleting Agent Tetrabenazine and Increases Progressive Ratio Responding
dc.contributor.author | Rotolo, Renee | |
dc.contributor.author | Dragacevic, Vladimir | |
dc.contributor.author | Kalaba, Predrag | |
dc.contributor.author | Urban, Ernst | |
dc.contributor.author | Zehl, Martin | |
dc.contributor.author | Roller, Alexander | |
dc.contributor.author | Wackerlig, Judith | |
dc.contributor.author | Langer, Thierry | |
dc.contributor.author | Pistis, Marco | |
dc.contributor.author | De Luca, Maria Antonietta | |
dc.contributor.author | Caria, Francesca | |
dc.contributor.author | Schwartz, Rebecca | |
dc.contributor.author | Presby, Rose | |
dc.contributor.author | Yang, Jen-Hau | |
dc.contributor.author | Samels, Shanna | |
dc.contributor.author | Correa, Merce | |
dc.contributor.author | Lubec, Gert | |
dc.contributor.author | Salamone, John | |
dc.date.accessioned | 2019-12-10T11:49:34Z | |
dc.date.available | 2019-12-10T11:49:34Z | |
dc.date.issued | 2019-06-28 | |
dc.identifier.citation | ROTOLO, Renee;DRAGACEVIC, Vladimir; KALABA, Predrag; URBAN, Ernst; ZEHL, Martin; ROLLER, Alexander; WACKERLIG, Judith; LANGER, Thierry; PISTIS, Marco; DE LUCA, Maria Antonietta; CARIA, Francesca; SCHWARTZ, Rebecca; PRESBY, Rose; YANG, Jen-Hau; SAMELS, Shanna; CORREA SANZ, Mercé; LUBEC, Gert; SALAMONE, John D. (2019). The Novel Atypical Dopamine Uptake Inhibitor (S)-CE-123 Partially Reverses the Effort-Related Effects of the Dopamine Depleting Agent Tetrabenazine and Increases Progressive Ratio Responding. Frontiers in Pharmacology, v. 10 | ca_CA |
dc.identifier.uri | http://hdl.handle.net/10234/185349 | |
dc.description.abstract | Animal studies of effort-based choice behavior are being used to model effort-related motivational dysfunctions in humans. With these procedures, animals are offered a choice between high-effort instrumental actions leading to highly valued reinforcers vs. low effort/ low reward options. Several previous studies have shown that dopamine (DA) uptake inhibitors, including GBR12909, lisdexamfetamine, methylphenidate, and PRX-14040, can reverse the effort-related effects of the vesicular monoamine transport blocker tetrabenazine, which inhibits DA storage. Because many drugs that block DA transport act as major stimulants that also release DA, and produce a number of undesirable side effects, there is a need to develop and characterize novel atypical DA transport inhibitors. (S)-CE-123 ((S)-5-((benzhydrylsulfnyl) methyl)thiazole) is a recently developed analog of modafnil with the biochemical characteristics of an atypical DA transport blocker. The present paper describes the enantioselective synthesis and initial chemical characterization of (S)-CE-123, as well as behavioral experiments involving effort-based choice and microdialysis studies of extracellular DA. Rats were assessed using the fxed ratio 5/chow feeding choice test. Tetrabenazine (1.0 mg/kg) shifted choice behavior, decreasing lever pressing and increasing chow intake. (S)-CE-123 was coadministered at doses ranging from 6.0 to 24.0 mg/kg, and the highest dose partially but signifcantly reversed the effects of tetrabenazine, although this dose had no effect on fxed ratio responding when administered alone. Additional experiments showed that (S)-CE-123 signifcantly increased lever pressing on a progressive ratio/chow feeding choice task and that the effective dose (24.0 mg/kg) increased extracellular DA in nucleus accumbens core. In summary, (S)-CE-123 has the behavioral and neurochemical profle of a compound that can block DA transport, reverse the effort-related effects of tetrabenazine, and increase selection of high-effort progressive ratio responding. This suggests that (S)-CE- 123 or a similar compound could be useful as a treatment for effort-related motivational dysfunction in humans. | ca_CA |
dc.format.extent | 12 p. | ca_CA |
dc.format.mimetype | application/pdf | ca_CA |
dc.language.iso | eng | ca_CA |
dc.publisher | Frontiers Media | ca_CA |
dc.relation.isPartOf | Frontiers in Pharmacology (2019), v. 10 | ca_CA |
dc.rights | Atribución 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-sa/4.0/ | * |
dc.subject | Dopamine | ca_CA |
dc.subject | Transport | ca_CA |
dc.subject | Synthesis | ca_CA |
dc.subject | Motivation | ca_CA |
dc.subject | Depression | ca_CA |
dc.subject | Fatigue | ca_CA |
dc.subject | Anergia | ca_CA |
dc.subject | Modafnil | ca_CA |
dc.title | The Novel Atypical Dopamine Uptake Inhibitor (S)-CE-123 Partially Reverses the Effort-Related Effects of the Dopamine Depleting Agent Tetrabenazine and Increases Progressive Ratio Responding | ca_CA |
dc.type | info:eu-repo/semantics/article | ca_CA |
dc.identifier.doi | https://doi.org/10.3389/fphar.2019.00682 | |
dc.relation.projectID | Fondazione di Sardegna (Esercizio finanziario 2017), FIR 2019, Fondo di Sviluppo e Coesione 2014-2020(Project RASSR03071; CUP F76C18000830002). | ca_CA |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | ca_CA |
dc.relation.publisherVersion | https://www.frontiersin.org/articles/10.3389/fphar.2019.00682/full | ca_CA |
dc.contributor.funder | 1) University of Connecticut Research Foundation; 2) Connecticut Institute for Brain and Cognitive Sciences and the Summer Undergraduate Research Fund at the University of Connecticut; 3) University of Connecticut Psychological Sciences Department; | ca_CA |
dc.type.version | info:eu-repo/semantics/publishedVersion | ca_CA |
Ficheros en el ítem
Este ítem aparece en la(s) siguiente(s) colección(ones)
-
PSB_Articles [1315]
Articles de publicacions periòdiques