Differential CNS sensitivity to PIA and theophylline in long-sleep and short-sleep mice

Long sleep (LS) and short sleep (SS) mice have a differential sensitivity to the behavioral actions of an adenosine agonist, R-phenylisopropyl-adenosine (PIA) that parallels their differential sensitivity to the soporific effects of ethanol. In addition to being more sensitive to the sedative effects of PIA, LS mice also show a greater excitatory response to an adenosine antagonist, theophylline (1,3-dimethylxanthine). The brain concentrations of both PIA and theophylline following drug administration do not differ in LS and SS mice, suggesting that the central nervous system of the LS mouse is more sensitive to both adenosine receptor agonists and antagonists. However, LS and SS mice made tolerant to ethanol did not show cross-tolerance to PIA. These results suggest that genetic selection for ethanol sensitivity has resulted in a parallel CNS sensitivity to purinergic drugs, but that acute alterations in sensitivity due to the development of ethanol tolerance do not involve changes in purinergic systems.