The dopamine depleting agent tetrabenazine alters effort-related decision making as assessed by mouse touchscreen procedures
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https://doi.org/10.1007/s00213-020-05578-w |
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Título
The dopamine depleting agent tetrabenazine alters effort-related decision making as assessed by mouse touchscreen proceduresAutoría
Fecha de publicación
2020Editor
SpringerISSN
0033-3158; 1432-2072Cita bibliográfica
ang, J., Presby, R.E., Rotolo, R.A. et al. The dopamine depleting agent tetrabenazine alters effort-related decision making as assessed by mouse touchscreen procedures. Psychopharmacology (2020). https://doi.org/10.1007/s00213-020-05578-wTipo de documento
info:eu-repo/semantics/articleVersión de la editorial
https://link.springer.com/article/10.1007/s00213-020-05578-wVersión
info:eu-repo/semantics/publishedVersionPalabras clave / Materias
Resumen
Rationale Effort-based decision-making tasks allow animals to choose between preferred reinforcers that require high effort to
obtain vs. low-effort/low reward options. Mesolimbic dopamine (DA) and related neural ... [+]
Rationale Effort-based decision-making tasks allow animals to choose between preferred reinforcers that require high effort to
obtain vs. low-effort/low reward options. Mesolimbic dopamine (DA) and related neural systems regulate effort-based choice.
Tetrabenazine (TBZ) is a vesicular monoamine transport type-2 inhibitor that blocks DA storage and depletes DA. In humans,
TBZ induces motivational dysfunction and depression. TBZ has been shown reliably to induce a low-effort bias in rats, but there
are fewer mouse studies.
Objectives The present studies used touchscreen operant procedures (Bussey-Saksida chambers) to assess the effects of TBZ on
effort-based choice in mice.
Methods C57BL6 mice were trained to press an elevated lit panel on the touchscreen on a fixed ratio 1 schedule reinforced by
strawberry milkshake, vs. approaching and consuming a concurrently available but less preferred food pellets (Bio-serv).
Results TBZ (2.0–8.0 mg/kg IP) shifted choice, producing a dose-related decrease in panel pressing but an increase in pellet
intake. In contrast, reinforcer devaluation by pre-feeding substantially decreased both panel pressing and pellet intake. In freefeeding choice tests, mice strongly preferred the milkshake vs. the pellets, and TBZ had no effect on milkshake intake or
preference, indicating that the TBZ-induced low-effort bias was not due to changes in primary food motivation or preference.
TBZ significantly decreased tissue levels of nucleus accumbens DA.
Conclusion The DA depleting agent TBZ induced an effort-related motivational dysfunction in mice, which may have clinical
relevance for assessing novel drug targets for their potential use as therapeutic agents in patients with motivation impairments. [-]
Publicado en
Psychopharmacology (2020).Proyecto de investigación
MINECO (PSI2015-68497- R)Derechos de acceso
© Springer-Verlag GmbH Germany, part of Springer Nature 2020
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