In vitro actions of ketamine and methohexitone in the rat hippocampus

The effects of ketamine and methohexitone have been tested in vitro on rat CA1 pyramidal neurones using conventional extracellular and intracellular recording techniques. Ketamine 20-200 mumol litre-1 predominantly increased excitability by a postsynaptic action: it enhanced the amplitude of the antidromic (field) potential response in extracellular recordings; in intracellular studies depolarized or did not change the resting membrane potential; increased intrinsic excitability (assessed by direct stimulation); and reduced accommodation properties of CA1 neurones. Methohexitone 10-100 mumol litre-1 did not affect the amplitude of the antidromic field potential responses, tended to hyperpolarize and reduce the intrinsic excitability, but did not alter accommodation properties. At these concentrations these agents either did not affect or, in the case of ketamine, enhanced excitatory synaptic transmission on to the CA1 pyramidal neurones. Methohexitone 50 and 100 mumol litre-1 also induced a large, slow (several seconds) after depolarization which followed the conventional orthodromic response and may lead to action potential discharge. It is clear that these agents have multiple actions on CA1 pyramidal neurones in vitro and that ketamine and methohexitone in vitro influence excitability by different mechanisms.