A cholinergic mechanism involved in fetal breathing during the high voltage ECoG state

The effects of muscarininc cholinergic neurotransmission on fetal breathing was determined by administration of carbachol or carbachol plus a muscarinic receptor antagonist into the cerebrospinal fluid of the fourth ventricle in unanesthetized fetal sheep. In the hour following the instillation of carbachol (1.0 μg), the incidence of fetal breathing in high voltage electrocortical state (ECoG) increased to 63 ± 11.7 (SEM) percent compared to 1.2 ± 0.9 after instillation of vehicle (Ringer solution). The cholinergic agonist increased breath amplitude from 4.5 ± 0.4 to 10.6 ± 1.4 mmHg. These effects were eliminated when the M₁ receptor antagonist pirenzipine (50-100 μg) was administered with carbachol but not by antagonists which are relatively selective for M₂ or M₃ receptors. When administered alone, muscarinic receptor antagonists did not effect the incidence or amplitude of fetal breathing in low voltage. These data indicate that the apnea which occurs during high voltage in the sheep fetus involves an inhibition of acetylcholine acting at M₁ muscarinic receptor bearing neurons.