Background: Apathy is frequently observed in numerous neurological disorders, including Alzheimer�s and\r\nParkinson�s, as well as neuropsychiatric disorders including schizophrenia. Apathy is defined as a lack of motivation\r\ncharacterized by diminished goal-oriented behavior and self-initiated activity. This study evaluated a chronic\r\nrestraint stress (CRS) protocol in modeling apathetic behavior, and determined whether administration of an\r\nanticholinesterase had utility in attenuating CRS-induced phenotypes.\r\nMethods: We assessed behavior as well as regional neuronal activity patterns using FosB immunohistochemistry\r\nafter exposure to CRS for 6 h/d for a minimum of 21 d. Based on our FosB findings and recent clinical trials, we\r\nadministered an anticholinesterase to evaluate attenuation of CRS-induced phenotypes.\r\nResults: CRS resulted in behaviors that reflect motivational loss and diminished emotional responsiveness. CRSexposed\r\nmice showed differences in FosB accumulation, including changes in the cholinergic basal forebrain\r\nsystem. Facilitating cholinergic signaling ameliorated CRS-induced deficits in initiation and motivational drive and\r\nrescued immediate early gene activation in the medial septum and nucleus accumbens.\r\nConclusions: Some CRS protocols may be useful for studying deficits in motivation and apathetic behavior.\r\nAmelioration of CRS-induced behaviors with an anticholinesterase supports a role for the cholinergic system in\r\nremediation of deficits in motivational drive
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