Neuropeptide Y reduces epileptiform discharges and excitatory synaptic transmission in rat frontal cortex in vitro

Neuropeptide Y reduced spontaneous and stimulation-evoked epileptiform disc harges in rat frontal cortex slices perfused with a magnesium-free solution and with the GABA(A) receptor antagonist picrotoxin. To investigate the me chanism of that action, effects of neuropeptide Y on intrinsic membrane pro perties and synaptic responses of layer II/III cortical neurons were studie d using intracellular recording. Neuropeptide Y (1 mu M) had no detectable effect on the membrane properties of neurons. The evoked synaptic potential s were attenuated by neuropeptide Y. Moreover, the pharmacologically isolat ed excitatory postsynaptic potentials, mediated by N-methyl-D-aspartate and non-N-methyl-D-aspartate receptors, were reversibly depressed by neuropept ide Y. The most pronounced inhibitory effect of neuropeptide Y was observed on late polysynaptic excitatory postsynaptic potentials. To assess a putat ive postsynaptic action of neuropeptide Y, N-methyl-D-aspartate was locally applied in the presence of tetrodotoxin. The N-methyl-D-aspartate-evoked d epolarizations were unaffected by neuropeptide Y, which suggests that the d epression of excitatory postsynaptic potentials was due to an action at sit es presynaptic to the recorded neurons. These data show that neuropeptide Y attenuates epileptiform discharges and the glutamate receptor-mediated synaptic transmission in the rat frontal co rtex. The above results indicate that neuropeptide Y may regulate neuronal excitability within the cortex, and that neuropeptide Y receptors are poten tial targets for an anticonvulsant therapy. (C) 2000 IBRO. Published by Els evier Science Ltd.