Evidence for an apathy phenotype in aged mice

Abstract

Apathy is widely reported in patients with neurological disorders or post viral infection but is also seen in otherwise-healthy aged individuals. This study investigated whether aged mice express behavioural and physiological changes indicative of an apathy phenotype. Using measures of motivation to work for reward, we found deficits in the progressive ratio task related to rate of responding. In an effort for reward task, aged mice were less willing to exert effort for high value reward. Aged mice exhibited reduced reward sensitivity and expressed lower measures of anxiety in the novelty supressed feeding test. In a test of cognition (novel object recognition) aged mice showed no impairments but activity was lower in a measure of exploration in a novel environment. Aged mice also showed an attenuated response to restraint stress with lower corticosterone and reduced paraventricular nucleus c-fos activation. Together, these data suggest aged mice show reduced goal-directed behaviour and reduced reward sensitivity and stress reactivity, reflective of emotional blunting and may be a suitable model for pre-clinical apathy research.Competing Interest StatementThe authors have declared no competing interest.AbbreviationsBLAbasolateral amygdalaCeAcentral amygdalaCORTcorticosteroneEBDMeffort-based decision makingEfReffort for rewardESElectrosprayHLPChigh performance liquid chromatographyMSmass spectrometryNORTnovel object recognition testNSFTnovelty supressed feeding testPRprogressive ratioPVNparaventricular nucleus of the hypothalamusSPTsucrose preference testView Full Text