PMID- 24305809
OWN - NLM
STAT- MEDLINE
DCOM- 20140131
LR  - 20240327
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 33
IP  - 49
DP  - 2013 Dec 4
TI  - Effort-related motivational effects of the VMAT-2 inhibitor tetrabenazine: 
      implications for animal models of the motivational symptoms of depression.
PG  - 19120-30
LID - 10.1523/JNEUROSCI.2730-13.2013 [doi]
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.
FAU - Nunes, Eric J
AU  - Nunes EJ
AD  - Department of Psychology, University of Connecticut, Storrs, Connecticut 
      06269-1020, Universitat Bonn, Pharma-Zentrum Bonn, Pharmazeutisches Institut, 
      Pharmazeutische Chemie, 53121 Bonn, Germany, and Area de Psicobiologia, Campus de 
      Riu Sec, Universitat Jaume I, 12071 Castello, Spain.
FAU - Randall, Patrick A
AU  - Randall PA
FAU - Hart, Evan E
AU  - Hart EE
FAU - Freeland, Charlotte
AU  - Freeland C
FAU - Yohn, Samantha E
AU  - Yohn SE
FAU - Baqi, Younis
AU  - Baqi Y
FAU - Muller, Christa E
AU  - Muller CE
FAU - Lopez-Cruz, Laura
AU  - Lopez-Cruz L
FAU - Correa, Merce
AU  - Correa M
FAU - Salamone, John D
AU  - Salamone JD
LA  - eng
GR  - R03 MH094966/MH/NIMH NIH HHS/United States
GR  - MH094966/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Adenosine A2 Receptor Antagonists)
RN  - 0 (Adrenergic Uptake Inhibitors)
RN  - 0 (Antidepressive Agents, Second-Generation)
RN  - 0 (Dopamine and cAMP-Regulated Phosphoprotein 32)
RN  - 0 (Enkephalins)
RN  - 0 (MSX 3 compound)
RN  - 0 (Ppp1r1b protein, rat)
RN  - 0 (Proto-Oncogene Proteins c-fos)
RN  - 0 (Slc18a2 protein, rat)
RN  - 0 (Vesicular Monoamine Transport Proteins)
RN  - 0 (Xanthines)
RN  - 01ZG3TPX31 (Bupropion)
RN  - 33507-63-0 (Substance P)
RN  - VTD58H1Z2X (Dopamine)
RN  - Z9O08YRN8O (Tetrabenazine)
SB  - IM
MH  - Adenosine A2 Receptor Antagonists/pharmacology
MH  - Adrenergic Uptake Inhibitors/antagonists & inhibitors/*pharmacology
MH  - Animals
MH  - Antidepressive Agents, Second-Generation/pharmacology
MH  - Behavior, Animal/drug effects
MH  - Bupropion/pharmacology
MH  - Conditioning, Operant/drug effects
MH  - Depression/*psychology
MH  - Disease Models, Animal
MH  - Dopamine/metabolism
MH  - Dopamine and cAMP-Regulated Phosphoprotein 32/metabolism
MH  - Enkephalins/metabolism
MH  - Feeding Behavior/drug effects
MH  - Immunohistochemistry
MH  - Male
MH  - Microdialysis
MH  - Motivation/*drug effects
MH  - Nucleus Accumbens/drug effects/metabolism
MH  - Proto-Oncogene Proteins c-fos/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Substance P/metabolism
MH  - Tetrabenazine/antagonists & inhibitors/*pharmacology
MH  - Vesicular Monoamine Transport Proteins/*antagonists & inhibitors
MH  - Xanthines/pharmacology
PMC - PMC3850037
OTO - NOTNLM
OT  - DAT inhibitor
OT  - basal ganglia
OT  - decision making
OT  - motivation
OT  - negative symptoms
OT  - vigor
EDAT- 2013/12/07 06:00
MHDA- 2014/02/01 06:00
PMCR- 2014/06/04
CRDT- 2013/12/06 06:00
PHST- 2013/12/06 06:00 [entrez]
PHST- 2013/12/07 06:00 [pubmed]
PHST- 2014/02/01 06:00 [medline]
PHST- 2014/06/04 00:00 [pmc-release]
AID - 33/49/19120 [pii]
AID - 2730-13 [pii]
AID - 10.1523/JNEUROSCI.2730-13.2013 [doi]
PST - ppublish
SO  - J Neurosci. 2013 Dec 4;33(49):19120-30. doi: 10.1523/JNEUROSCI.2730-13.2013.