Molecular Connections between Arousal and Metabolic Disease: Orexin and Modafinil; Annual rept. 27 Mar 2007-26 Mar 2008

摘要

Obesity and metabolic diseases are known to be tightly linked to arousal-sleep cycles. Further both metabolic disease and arousal are known to have significant impacts on cognitive function in humans and animals. Importantly the armed forces represent a population at significant risk for increased stress and disrupted arousal-sleep cycles. Because the incidence of metabolic disease and obesity is increasing even in these physically fit individuals understanding the interactions between these systems is highly significant. Further some anti-fatigue pharmacologies (e.g. modafinil) are already used in military settings though their long-term effects on metabolism or central nervous system function are not well-understood. We have completed Year 2 of the proposed funding period to assess the physiological and behavioral effects of this pharmacology on rat subjects and identify potential molecular mechanisms activated by nutrients. Our data demonstrate that chronic administration of intraperitoneal modafinil does not alter dietary induced obesity or impair glucose tolerance. Additionally we observed that chronic central modafinil does not increase stress in rats but does attenuate object recognition memory. Ongoing studies are assessing the effects of pharmacological inhibition or activation of a potential molecular mechanism mTOR.