Nitric oxide mediated recovery sleep is attenuated with aging

Nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) in the cholinergic basal forebrain (BF) during sleep deprivation (SD) is implicated in adenosine (AD) release and induction of recovery sleep. Aging is associated with impairments in sleep homeostasis, such as decrease in non-rapid eye movement sleep (NREM) intensity following SD. We hypothesized that age related changes in sleep homeostasis may be induced by impairments in NO-mediated sleep induction. To test this hypothesis we measured levels of NO and iNOS in the BF during SD as well as recovery sleep after SD and NO-donor (DETA/NO) infusion into the BF in three age groups of rats (young, 4 months; middle-aged, 14 months; old, 24 months). We found that in aged rats as compared to young (1) recovery NREM sleep intensity was significantly decreased, (2) neither iNOS nor NO increased in the BF during SD, and (3) DETA/NO infusion failed to induce sleep. Together, these results support our hypothesis that aging impairs the mechanism through which NO in the BF induces sleep.