The adenosine A1-receptor antagonist 8-CPT reverses ethanol-induced inhibition of fetal breathing movements

Abstract

Administration of either ethanol or adenosine inhibits fetal breathing movements (FBM), eye movements, and low-voltage electrocortical activity (LV ECoG). The concentration of adenosine in ovine fetal cerebral extracellular fluid increases during ethanol-induced inhibition of FBM. The purpose of this study was to determine the effect of a selective adenosine A1-receptor antagonist, 8-cyclopentyltheophylline (8-CPT) on the incidence of FBM during ethanol exposure. After a 2-h control period, seven pregnant ewes received a 1-h intravenous infusion of ethanol (1 g/kg maternal body wt), followed 1 h later by a 2-h fetal intravenous infusion of either 8-CPT (3.78 ± 0.08 μg ⋅ kg−1 ⋅ min−1) or vehicle. Ethanol reduced the incidence of FBM from 44.0 ± 10.4 to 2.7 ± 1.3% ( P < 0.05) and 51.2 ± 7.6 to 11.9 ± 5.0% ( P < 0.05) in fetuses destined to receive 8-CPT or vehicle, respectively. In the vehicle group, FBM remained suppressed for 7 h. In contrast, during the first hour of 8-CPT infusion, FBM returned to baseline (31 ± 11%) and was not different from control throughout the rest of the experiment. Ethanol also decreased the incidence of both low-voltage electrocortical activity and eye movements, but there were no differences in the incidences of these behavioral parameters between the 8-CPT and vehicle groups throughout the experiment. These data are consistent with the hypothesis that adenosine, acting via A1 receptors, may play a role in the mechanism of ethanol-induced inhibition of FBM.