Sleep deprivation upregulates A1 adenosine receptors in the rat basal forebrain

Sleep deprivation increases the levels of extracellular adenosine and A1 receptor (A1R)mRNA in the cholinergic zone of the basal forebrain, a region involved in sleep homeostasis. To evaluate homeostatic control mechanisms, we examined the sleep deprivation-induced changes in the A1R density in rodent brain using [H]CPFPX receptor autoradiography. We also examined the role of nuclear factor-kappaB (NF-kappaB) in transcriptional upregulation of A1R mRNA by use of the inhibitor peptide SN50 to inhibit nuclear translocation of NF-kappaB. We found a significant increase in cholinergic basal forebrain A1R density following 24 h of sleep deprivation and evidence that the upregulation of A1R is mediated by NF-kappaB. The A1R increase may be important in sleep homeostasis, since the increase in A1R density would increase the inhibitory effect of given level of adenosine, thus increasing the gain of the homeostat.