We have studied the effects of orexin-A on NMDA component of registered field potentials in pyramidal (str. pyramidale) and radial layers (st. radiatum) of CA-1 field of the hippocampus. To facilitate generation of NMDA responses in vitro experiments were performed in Mg(2+)- free solution. From field excitatory postsynaptic potential (EPSP), which was induced by stimulation of Schaffer collaterals, NMDA component was isolated using modified physiological solution: bicuculline metiodide (20-40 microM) and CNQX (5 microM) were eddied for removing GABA-ergic inhibition and blocking AMPA-glutamatergic receptor-mediated responses, respectively. Application of orexin-A (100 nM, for 5 -15 min) evoked inhibition of NMDA component of population spike (84.4+/-5%, n=7) and long-term depression of isolated NMDA component of field EPSP, which was made up (77.7+/-2.8%, n=12) comparing with control after 45 min of orexin-A application. Orexin-A mediated depression starts after 7-10 min of application, which is sufficient for NE release from adrenergic terminals in the hippocampus. As the agonist of alpha-adrenoreceptors clonidine completely mimicked the effects of orexin-A possible involvement of adrenergic system of the brain in these effects are considered.
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