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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 19120-19130 |
| Number of pages | 11 |
| Journal | Journal of Neuroscience |
| Volume | 33 |
| Issue number | 49 |
| DOIs | |
| State | Published - Dec 9 2013 |
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All Science Journal Classification (ASJC) codes
- Neuroscience(all)
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Effort-related motivational effects of the VMAT-2 inhibitor tetrabenazine : Implications for animal models of the motivational symptoms of depression. / Nunes, Eric J.; Randall, Patrick A.; Hart, Evan E.; Freeland, Charlotte; Yohn, Samantha E.; Baqi, Younis; Müller, Christa E.; López-Cruz, Laura; Correa, Mercè; Salamone, John D.
In: Journal of Neuroscience, Vol. 33, No. 49, 09.12.2013, p. 19120-19130.Research output: Contribution to journal › Article
TY - JOUR
T1 - Effort-related motivational effects of the VMAT-2 inhibitor tetrabenazine
T2 - Implications for animal models of the motivational symptoms of depression
AU - Nunes, Eric J.
AU - Randall, Patrick A.
AU - Hart, Evan E.
AU - Freeland, Charlotte
AU - Yohn, Samantha E.
AU - Baqi, Younis
AU - Müller, Christa E.
AU - López-Cruz, Laura
AU - Correa, Mercè
AU - Salamone, John D.
PY - 2013/12/9
Y1 - 2013/12/9
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84888998855&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.2730-13.2013
DO - 10.1523/JNEUROSCI.2730-13.2013
M3 - Article
C2 - 24305809
AN - SCOPUS:84888998855
VL - 33
SP - 19120
EP - 19130
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 49
ER -