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Ghrelin induced memory facilitation implicates nitric oxide synthase activation and decrease in the threshold to promote LTP in hippocampal dentate gyrus
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
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2010 (English)In: Physiology and Behavior, ISSN 0031-9384, E-ISSN 1873-507X, Vol. 101, no 1, 117-123 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2010. Vol. 101, no 1, 117-123 p.
Keyword [en]
Ghrelin, Memory consolidation, Long-term potentiation, Nitric oxide synthase, Hippocampus
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-135059DOI: 10.1016/j.physbeh.2010.04.026ISI: 000280118300016PubMedID: 20451534OAI: oai:DiVA.org:uu-135059DiVA: diva2:374330
Available from: 2010-12-03 Created: 2010-12-03 Last updated: 2010-12-08Bibliographically approved

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