Local anaesthetic actions of cocaine: effects on excitatory and inhibitory synaptic responses in the hippocampus in vitro.

1. The basis for the proconvulsant action of cocaine was investigated in the CA1 region of the rat hippocampal slice in vitro. 2. Superfusion with 100 microM cocaine depressed inhibitory and excitatory postsynaptic potentials recorded intracellularly from CA1 pyramidal neurones; both types of potentials were inhibited to an equal extent. When inhibition was assessed using extracellular recording of population spike responses before and after conditioning impulses, there did not appear to be any selective effect upon either recurrent or feed-forward gamma-aminobutyric acid (GABA)ergic inhibition. 3. Not all responses showed equivalent sensitivity to the local anaesthetic actions of cocaine. In particular, the antidromic population spike evoked by stimulation of the alveus was significantly more sensitive than the presynaptic fibre spike elicited by stimulation of stratum radiatum. 4. The rate of interictal spiking in hippocampus, induced by penicillin and increased potassium in the perfusion medium, was depressed by superfusion with cocaine in the range 5-100 microM. 5. These results suggest that cocaine does not have a selective depressant effect upon inhibitory pathways in the CA1 region of the hippocampus. Although the hippocampus shows epileptiform activity following systemic administration of local anaesthetics such as cocaine in the intact rat, this effect may not reflect a direct hippocampal site of drug action.