Linopirdine reduces stimulus intensity threshold for induction of long-term potentiation in the Schaffer collateral/CA1 pathway in rat hippocampal slices.

Linopirdine, a putative cognition enhancing agent, increases neurotransmitter release and blocks M-current in rat brain. Its effects on long-term potentiation (LTP) in the Schaffer collateral/CA1 pathway were investigated using standard, extracellular recording techniques in rat hippocampal slice preparation. When using a half maximal stimulus intensity for tetanic stimulation, a 30 min exposure to 3 or 10 microM linopirdine exerted no significant effect on excitatory postsynaptic potential (EPSP) slope, post-tetanic potentiation or LTP. In contrast, when a weak stimulus was employed, linopirdine enhanced the incidence and amplitude of LTP in a dose-dependent manner. These results indicate that linopirdine reduced stimulus intensity threshold for induction of LTP, an effect which may be mediated by its ability to enhance presynaptic glutamate release and cause CA1 membrane depolarization.