On the mechanism of barbiturate anaesthesia

1. The effects of pentobarbitone (0·05–0·6 m M in saline solution) on the evoked field potentials of in vitro preparations of guinea‐pig olfactory cortex were studied. 2. The evoked field potentials comprised an initial diphasic wave — the lateral olfactory tract (l.o.t.) compound action potential — followed by a surface negative wave (e.p.s.p) of 1–3 mV amplitude and about 10 msec duration. Superimposed on the negative wave were a number of positive peaks (population spikes). 3. Pentobarbitone depressed the e.p.s.p. but not the l.o.t. compound action potential. The number and size of the population spikes were progressively reduced as the e.p.s.p. became depressed, indicating a failure of transmission through the cortical relay. The e.p.s.p. depression increased with increasing concentrations of pentobarbitone. 4. Pentobarbitone had no effect on the threshold to electrical stimulation of the l.o.t. fibres or on that of the post‐synaptic cells to synaptic excitation. 5. Post‐tetanic potentiation and frequency potentiation were either of normal magnitude or were enhanced in the presence of 0·2–0·3 m M pentobarbitone. 6. It is concluded that pentobarbitone probably reduces the output of transmitter from the presynaptic nerve terminals of the olfactory cortex and that this mechanism could be the basis of the depressant action of the barbiturates.