Effects of substance P and its antagonist L-733060 on long term potentiation in guinea pig hippocampal slices

The neuropeptide substance P (SP) has been suggested to be involved in several physiological and pathological conditions including learning and memory and the processing of pain. This study investigated for the first time acute effects of SP and the neurokinin-1 (NK-1) receptor antagonist L-733060 on long term potentiation (LTP) in the hippocampus. Electrically evoked fEPSP was tested under the influence of SP in the CA1 region of the guinea pig hippocampus. Concentrations of 1 and 10 μM SP increased fEPSP slopes to 114.3±4.5% and 115.8±2.7%, respectively. A threshold concentration was found at 0.1 μM SP. The SP-specific NK-1 receptor antagonist L-733060 did not influence fEPSP in a concentration of 1 μM. In experiments with LTP, a significant increase of potentiations after 60 min was seen with 1 μM SP. Even if the initial baseline increase due to SP (1 μM) was subtracted, potentiations were bigger compared to controls. L-733060 (1 μM) suppressed the excitatory effects of 1 μM SP nearly complete and subsequent induced LTP was not increased. In conclusion, SP has excitatory effects in the hippocampus and is able to facilitate LTP via activation of the NK-1 receptor.