Effort-related motivational effects of the VMAT-2 inhibitor tetrabenazine: Implications for animal models of the motivational symptoms of depression

Eric J. Nunes, Patrick A. Randall, Evan E. Hart, Charlotte Freeland, Samantha E. Yohn, Younis Baqi, Christa E. Müller, Laura López-Cruz, Mercè Correa, John D. Salamone

نتاج البحث: المساهمة في مجلةمراجعة النظراء

93 اقتباسات (Scopus)

ملخص

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.

اللغة الأصليةEnglish
الصفحات (من إلى)19120-19130
عدد الصفحات11
دوريةJournal of Neuroscience
مستوى الصوت33
رقم الإصدار49
المعرِّفات الرقمية للأشياء
حالة النشرPublished - 2013
منشور خارجيًانعم

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