Purinergic modulation of ethanol-induced sleep time in long-sleep and short-sleep mice

Abstract

The long-sleep (LS) and short-sleep (SS) mice were selectively bred for differences in sensitivity to the depressant effects of ethanol. In addition to their differential sensitivity to ethanol, they are also differentially sensitive to purinergic agonists and antagonists. This suggests that there may be differences in the purinergic systems of these lines of mice which may aid in understanding how they differ in ethanol sensitivity. We have investigated whether these drugs are capable of modifying acute ethanol sensitivity as measured by ethanol-induced loss of the righting response (ethanol sleep time), waking blood and brain ethanol concentrations, and blood ethanol elimination rate. The purinergic agonists cyclohexyladenosine (CHA), L-phenylisopropyladenosine (PIA), 2-chloroadenosine (CAD), and N-ethylcarboxamidoadenosine (NEC) increased sleep time in both LS and SS mice, however, LS mice were generally more affected than SS. The LS and SS mice were also differentially sensitive to the purinergic antagonists, theophylline and caffeine. Blood and brain ethanol concentration on awakening suggested that CNS sensitivity to acute ethanol administration was altered by pretreatment with agonists but not antagonists. Two agonists, CHA and NEC, significantly lowered ethanol elimination in both lines of mice while PIA, CAD, and the antagonists theophylline, and caffeine were without affect on elimination rate. These data support previous observations that adenosine-mediated systems may be involved in the modulation of ethanol sensitivity.