Electrophysiology of the 5-HT1A ligand MDL 73005EF in the rat hippocampal slice.

The actions of 5-hydroxytryptamine (5-HT) and the 5-HT1A receptor ligand MDL 73005EF on neuronal activity in the CA1 region of rat hippocampal slices in vitro were recorded using intra- and extracellular recording techniques. 5-HT (1-30 microM) hyperpolarised the pyramidal neurones in a concentration-dependent manner and reduced membrane resistance and action potential after-hyperpolarisations (AHPs). MDL 73005EF (1-30 microM) had no clear effects on membrane potential, membrane resistance or AHPs. However, prior application of 3 microM MDL 73005EF to the slices for 10-60 min antagonised the hyperpolarisation induced by 30 microM 5-HT but not the reduction in spike AHP or the hyperpolarisation induced by the GABAB receptor agonist baclofen. MDL 73005EF and the 5-HT1A/2 receptor antagonist spiperone (both 3 microM) reduced the frequency and amplitude of spontaneous inhibitory (bicuculline-sensitive) postsynaptic potentials. Extracellular recordings of population action potentials revealed that MDL 73005EF did not prevent the induction or maintenance of hippocampal long-term potentiation or exhibit local anaesthetic properties. It is concluded that MDL 73005EF is an antagonist at 5-HT1A receptors on hippocampal CA1 pyramidal neurones.