GABAergic and glutamatergic effects on behaviour in fetal sheep

1. Studies were carried out in unanaesthetized fetal sheep at 125-135 days gestation to investigate neurotransmitters involved in behavioural state. 2. Catheters and electrodes were chronically placed to record tracheal and arterial pressure, electrocortical activity (ECoG), nuchal muscle activity and to instill drugs into the cerebrospinal fluid (CSF) of the fourth ventricle. 3. Administration of the N-methyl-D-aspartate receptor antagonists DL-2-amino-5-phosphopentanoic acid (AP5) or (+)-5-methyl-10,11-dihydro-5H-dibenzol[a,d]cyclohepten-5,10- iminemoleate (MK-801) increased the incidence of fetal behaviour characterized by low voltage ECoG, nuchal muscle activity and an increase in mean arterial blood pressure from 4.1 +/- 6 to 60.6 +/- 6.2% (mean +/- S.E.M.) (AP5; P = 0.003) and from 7.6 +/- 3.6 to 50.8 +/- 7.0% (MK-801; P = 0.004; values are expressed as the percentage of each 60 min period in which the state was present). 4. The incidence of fetal breathing during periods of low voltage (LV)-ECoG and nuchal muscle activity was 83.1 +/- 5.6%. The incidence of fetal breathing during LV-ECoG associated with nuchal muscle atonia was 63.1 +/- 5.0% before AP5 or MK-801 and 64.4 +/- 9.8% after instillation of these drugs. The amplitude of fetal breaths increased from 4.0 +/- 0.3 mmHg in low voltage ECoG periods to 6.7 +/- 0.8 mmHg (P = 0.006) during periods of low voltage with nuchal muscle activity. There was no significant change in breath timing during these periods.