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Behavioral and Brain Functions
Published in: Behavioral and Brain Functions 1/2012

Open Access 01-12-2012 | Research

Acetylcholinesterase inhibition ameliorates deficits in motivational drive

Authors: Keri Martinowich, Kathleen M Cardinale, Robert J Schloesser, Michael Hsu, Nigel H Greig, Husseini K Manji

Published in: Behavioral and Brain Functions | Issue 1/2012

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Abstract

Background

Apathy is frequently observed in numerous neurological disorders, including Alzheimer's and Parkinson's, as well as neuropsychiatric disorders including schizophrenia. Apathy is defined as a lack of motivation characterized by diminished goal-oriented behavior and self-initiated activity. This study evaluated a chronic restraint stress (CRS) protocol in modeling apathetic behavior, and determined whether administration of an anticholinesterase had utility in attenuating CRS-induced phenotypes.

Methods

We assessed behavior as well as regional neuronal activity patterns using FosB immunohistochemistry after exposure to CRS for 6 h/d for a minimum of 21 d. Based on our FosB findings and recent clinical trials, we administered an anticholinesterase to evaluate attenuation of CRS-induced phenotypes.

Results

CRS resulted in behaviors that reflect motivational loss and diminished emotional responsiveness. CRS-exposed mice showed differences in FosB accumulation, including changes in the cholinergic basal forebrain system. Facilitating cholinergic signaling ameliorated CRS-induced deficits in initiation and motivational drive and rescued immediate early gene activation in the medial septum and nucleus accumbens.

Conclusions

Some CRS protocols may be useful for studying deficits in motivation and apathetic behavior. Amelioration of CRS-induced behaviors with an anticholinesterase supports a role for the cholinergic system in remediation of deficits in motivational drive.
Appendix
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Metadata
Title
Acetylcholinesterase inhibition ameliorates deficits in motivational drive
Authors
Keri Martinowich
Kathleen M Cardinale
Robert J Schloesser
Michael Hsu
Nigel H Greig
Husseini K Manji
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Behavioral and Brain Functions / Issue 1/2012
Electronic ISSN: 1744-9081
DOI
https://doi.org/10.1186/1744-9081-8-15

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