Ghrelin induced memory facilitation implicates nitric oxide synthase activation and decrease in the threshold to promote LTP in hippocampal dentate gyrus.
Although the hypothalamus has been long considered the main ghrelin (Ghr) target organ mediating orexigenic effects, recently it has been shown that in-vivo Ghr hippocampus administration improves learning and memory in the inhibitory avoidance paradigm. However, the possible mechanisms underlying this memory facilitation effect have not been clarified. Given that the biochemical memory cascade into the hippocampus involves nitric oxide (NO) synthesis via NO synthase (NOS) activation, we investigated 1) if Ghr administration modulated NOS activity in the hippocampus; and 2) if hippocampal NOS inhibition influenced Ghr-induced memory facilitation, using a behavioral paradigm, biochemical determinations and an electrophysiological model. Our results showed that intra-hippocampal Ghr administration increased the NOS activity in a dose dependent manner, and reduced the threshold for LTP generation in dentate gyrus of rat hippocampus. Moreover, pre-administration of NG-nitro-l-arginine (l-NOArg) in the hippocampus partially prevented the Ghr-induced memory improvement, abolished the increase in NOS activity, and prevented the decreased threshold to generate LTP induced by Ghr. These findings suggest that activation of the NOS/NO pathway in hippocampus participates in the effects of Ghr on memory consolidation and is related with plastic properties of the hippocampal three-synaptic loop.
Carlini
Valeria P
VP
IFEC, CONICET, Departamento de Farmacología, Facultad de Ciencias Químicas, UNC, Córdoba, Argentina. vcarlini@mail.fcq.unc.edu.ar
Perez
Mariela F
MF
Salde
Estela
E
Schiöth
Helgi B
HB
Ramirez
Oscar A
OA
de Barioglio
Susana R
SR
D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D018891:Dentate Gyrus / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D054439:Ghrelin / Q000008:administration & dosage / Q000502:physiology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012044:Regression Analysis; D015290:Second Messenger Systems / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D054439:Ghrelin; D019001:Nitric Oxide Synthase