Effect of sleep deprivation on righting reflex in the rat is partially reversed by administration of adenosine A1 and A2 receptor antagonists

Background: Similarities between naturally occurring sleep and general anesthesia suggest that the two states may interact physiologically. The authors have previously demonstrated that sleep deprivation potentiates anesthetic-induced loss of righting reflex (LORR) in rats. One possible mediator for this effect is adenosine, which accumulates in the brains of sleep-deprived animals and reduces anesthetic requirements. The authors tested in rats the hypothesis that potentiating effects of sleep deprivation on LORR can be altered by adenosine A1 and A2a receptor antagonists. Methods: Five experiments were conducted. In each, rats underwent four trials, consisting of a 24-h period of either sleep deprivation or ad libitum activity followed by administration of a fixed dose of an adenosine antagonist or vehicle. Rats were then given isoflurane, and the time to LORR and recovery were measured. Each experiment tested a specific dose of an A1 receptor antagonist (8-cyclopentyltheophylline given via microinjection into the basal forebrain), an A2a receptor antagonist (ZM241385 via intraperitoneal administration), or both. in each experiment, all rats received all combinations of activity and drug/vehicle, separated by 5-7 days. Results: In rested rats, neither antagonist altered the time to LORR. In sleep-deprived rats, both ZM241385 and 8-cyclopentyltheophylline prolonged the time to LORR and shortened recovery in a dose-dependent manner. Prolongation also occurred when subtherapeutic doses of both agents were coadministered. Conclusion Both antagonists partially reversed the effect of sleep deprivation on anesthetic action. This result implies that deprivation-induced changes in adenosine receptor activity can alter LORR. Neither antagonist completely reversed this effect, suggesting possible non-adenosine-mediated effects of sleep deprivation.