Orexin-A induces long-term depression of nmda responses in CA-1 field of hippocampal slices.
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.
Doreulee
N
N
Iv. Javakhishvili Tbilisi State University, Faculty of Exact and Natural Sciences, Tbilisi, Georgia.
Alania
M
M
Chikovani
M
M
Chkhartishvili
B
B
Skhirtladze
C
C
D000818:Animals; D006624:Hippocampus / Q000187:drug effects*; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology*; D008297:Male; D009479:Neuropeptides / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D000068797:Orexins; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000502:physiology
D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D000068797:Orexins; D016194:Receptors, N-Methyl-D-Aspartate