Prolongation of hippocampal inhibitory postsynaptic potentials by barbiturates

IT is well documented that barbiturates dramatically prolong presynaptic inhibition 1–4 . Their effect on postsynaptic inhibition is less clear, although the available evidence suggests that a similar enhancement may occur at some sites 5–7 . Since the inhibitory postsynaptic potentials (i.p.s.p.s) in hippocampal neurones are unusually large and the neurones are readily penetrable by microelectrodes 8 , we have studied the effect of barbiturates on these i.p.s.p.s in detail. We have found that barbiturates hyperpolarise hippocampal neurones and markedly prolong the i.p.s.p. by a direct action on inhibitory synapses, anaesthetic doses increasing the duration fivefold. The hyperpolarising action of barbiturates and their effect on i.p.s.p.s would both contribute to the neural depressant action of these anaesthetic agents.