Neuropeptide Y reduces epileptiform discharges and excitatory synaptic transmission in rat frontal cortex in vitro.
Neuropeptide Y reduced spontaneous and stimulation-evoked epileptiform discharges in rat frontal cortex slices perfused with a magnesium-free solution and with the GABA(A) receptor antagonist picrotoxin. To investigate the mechanism of that action, effects of neuropeptide Y on intrinsic membrane properties and synaptic responses of layer II/III cortical neurons were studied using intracellular recording. Neuropeptide Y (1 microM) had no detectable effect on the membrane properties of neurons. The evoked synaptic potentials were attenuated by neuropeptide Y. Moreover, the pharmacologically isolated excitatory postsynaptic potentials, mediated by N-methyl-D-aspartate and non-N-methyl-D-aspartate receptors, were reversibly depressed by neuropeptide Y. The most pronounced inhibitory effect of neuropeptide Y was observed on late polysynaptic excitatory postsynaptic potentials. To assess a putative postsynaptic action of neuropeptide Y, N-methyl-D-aspartate was locally applied in the presence of tetrodotoxin. The N-methyl-D-aspartate-evoked depolarizations were unaffected by neuropeptide Y, which suggests that the depression of excitatory postsynaptic potentials was due to an action at sites 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 cortex. The above results indicate that neuropeptide Y may regulate neuronal excitability within the cortex, and that neuropeptide Y receptors are potential targets for an anticonvulsant therapy.
Bijak
M
M
Department of Physiology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343, Kraków, Poland.
D000818:Animals; D004594:Electrophysiology; D004827:Epilepsy / Q000503:physiopathology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005625:Frontal Lobe / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009478:Neuropeptide Y / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission
D009478:Neuropeptide Y