Demonstration of Central Nervous System Tolerance to Ethanol in Mice: Consequent Effects on Smooth Muscle in Vitro

Mice were given ethanol (9 g/kg) or saline (57 ml/kg) daily in three divided doses for periods of 1 and 4 days to study the effects of such ethanol (ETOH) exposure on central nervous system (CNS) and peripheral smooth muscle (vasa deferentia) function. After 1 day, ETOH‐treated mice were functionally tolerant to the hypothermic (3 g/kg, intraperitoneal), but not to the hypnotic (3.25 g/kg, intraperitoneal) effect of ETOH. Functional tolerance to both CNS effects of ETOH was demonstrated in mice after the 4‐day ETOH exposure. Norepinephrine (NE) and high K⁺‐depolarizing solutions each elicited dose‐dependent contractions in the mouse vasa deferens preparation in vitro that consisted of a phasic and tonic component. The tonic components of the NE and K⁺ responses were more dependent upon extracellular Ca²⁺ (Ca²⁺_ext) than the phasic components. Addition of ETOH (120 to 480 mM) or the Ca²⁺ channel‐antagonist nifedipine (1× 10+ to 3 × 10⁻‐⁷ m) to the preparation selectively inhibited the tonic component of the NE and K⁺ responses, suggesting that both agents acted to inhibit the responses by interfering with the translocation of Ca²⁺_ext. Vasa deferentia isolated from ETOH‐treated mice did not exhibit altered reactivity to NE in the phasic or tonic comp nent of the response. The isolated smooth muscle from mice centrally tolerant to ETOH did not appear to be tolerant to the inhibitory effect of ETOH or cross‐tolerant to the inhibitory effect of nifedipine on stimulant‐induced contractions.