Sleep deprivation upregulates A1 adenosine receptors in the rat basal forebrain

Sleep deprivation increases the levels of extracellular adenosine and A, receptor (A(1)R)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 A(1)R density in rodent brain using [H-3]CPFPX receptor autoradiography. We also examined the role of nuclear factor-kappa B (NF-kappa B) in transcriptional upregulation of A(1)R mRNA by use of the inhibitor peptide SN50 to inhibit nuclear translocation of NF-kappa B. We found a significant increase in cholinergic basal forebrain A(1)R density following 24 h of sleep deprivation and evidence that the upregulation of A(1)R is mediated by NF-kappa B. The A(1)R increase may be important in sleep homeostasis, since the increase in A(1)R density would increase the inhibitory effect of given level of adenosine, thus increasing the gain of the homeostat.