acetylcholinesterase inhibition ameliorates deficits in motivational drive乙酰胆碱酯酶的抑制改善赤字在动机驱动.pdfVIP

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acetylcholinesterase inhibition ameliorates deficits in motivational drive乙酰胆碱酯酶的抑制改善赤字在动机驱动.pdf

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acetylcholinesterase inhibition ameliorates deficits in motivational drive乙酰胆碱酯酶的抑制改善赤字在动机驱动

Martinowich et al. Behavioral and Brain Functions 2012, 8:15 /content/8/1/15 RESEARCH Open Access Acetylcholinesterase inhibition ameliorates deficits in motivational drive 1,3* 1 1 1 2 Keri Martinowich , Kathleen M Cardinale , Robert J Schloesser , Michael Hsu , Nigel H Greig and Husseini K Manji4 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