Effort-related motivational effects of the VMAT-2 inhibitor tetrabenazine: implications for animal models of the motivational symptoms of depression.
J Neurosci
; 33(49): 19120-30, 2013 Dec 04.
Article
em En
| MEDLINE
| ID: mdl-24305809
ABSTRACT
Motivated behaviors are often characterized by a high degree of behavioral activation, and work output and organisms frequently make effort-related decisions based upon cost/benefit analyses. Moreover, people with major depression and other disorders often show effort-related motivational symptoms such as anergia, psychomotor retardation, and fatigue. It has been suggested that tasks measuring effort-related choice behavior could be used as animal models of the motivational symptoms of depression, and the present studies characterized the effort-related effects of the vesicular monoamine transport (VMAT) inhibitor tetrabenazine. Tetrabenazine produces depressive symptoms in humans and, because of its selective inhibition of VMAT-2, it preferentially depletes dopamine (DA). Rats were assessed using a concurrent fixed-ratio 5/chow feeding choice task that is known to be sensitive to dopaminergic manipulations. Tetrabenazine shifted response choice in rats, producing a dose-related decrease in lever pressing and a concomitant increase in chow intake. However, it did not alter food intake or preference in parallel free-feeding choice studies. The effects of tetrabenazine on effort-related choice were reversed by the adenosine A2A antagonist MSX-3 and the antidepressant bupropion. A behaviorally active dose of tetrabenazine decreased extracellular DA in nucleus accumbens and increased expression of DARPP-32 in accumbens medium spiny neurons in a pattern indicative of reduced transmission at both D1 and D2 DA receptors. These experiments demonstrate that tetrabenazine, which is used in animal models to produce depression-like effects, can alter effort-related choice behavior. These studies have implications for the development of animal models of the motivational symptoms of depression and related disorders.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tetrabenazina
/
Inibidores da Captação Adrenérgica
/
Depressão
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Proteínas Vesiculares de Transporte de Monoamina
/
Motivação
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Neurosci
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Espanha