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1 Departments of Physiology and
Obstetrics and Gynecology,
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.
eye movements; 8-cyclopentyltheophylline; electrocortical activity; fetal sheep
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