URETHANE ANESTHESIA AS AN UNPARALLELED MODEL FOR NATURAL SLEEP

Urethane (ethyl carbamate), unlike other anesthetics, allows for sleep-like spontaneous alternations between NREM-like and REM-like activity states making it a powerful model for sleep cycles, and for sleep. Similarities include brain state electrography, timing of alternations, physiological correlates, pharmacology, brainstem reliance, as well as dependence on ambient temperature. We believe that urethane anesthesia is the most complete pharmacological model for the full spectrum of natural sleep. This suggests that the pharmacological action of urethane has parallels to the physiological regulation of sleep itself. If true, then adenosinergic drugs known to affect the sleep cycle should also affect state alternations under urethane. Male Sprague-Dawley rats were anesthetized with i.v. urethane and local field potential recordings were made from frontal cortex and hippocampus. Stable rhythmic state alternations were recorded before i.v. or i.c.v. administrations of adenosine, caffeine, N6-cyclopentyladenosine (CPA), or CGS 21680. We tracked changes in the spectral features of states and their alternations following drug administration. Adenosine, whether administered peripherally or centrally, promoted the deactivated (NREM-like) state. In contrast, caffeine (again either peripherally or centrally) decreased the NREM-like state. Interestingly, the A2A agonist CGS 21680 promoted the NREM-like state in a fashion similar to adenosine itself, but the A1 agonist CPA appeared to abolish state alternations altogether by promoting a highly deactivated state characterized by prominent and dense slow-waves. Adenosine and both its agonists and antagonists have parallel effects across urethane anesthesia and natural sleep. This is yet further evidence supporting the validity of the urethane model of sleep itself.