Behavioural effects and regulation of PKCα and MAPK by huprine X in middle aged mice

M. Ratia, L. Giménez-Llort, P. Camps, D. Muñoz-Torrero, M. V. Clos, A. Badia

Research output: Contribution to journalArticleResearchpeer-review

19 Citations (Scopus)

Abstract

The behavioural effects of huprine X, a new anticholinesterasic inhibitor, as well as its effects on the regulation of protein kinase C (PKC), mitogen activated protein kinase (MAPK) and α-secretase (ADAM10 and TACE/ADAM17) related to amyloid precursor protein (APP) processing remain to be established. In the present work, 12month old 126/Sv×C57b/6 male mice which received chronic i.p. treatment with either saline, huprine X (0.04μmolkg-1) or huprine X (0.12μmolkg-1), were submitted to a battery of behavioural tests and thereafter the brains were dissected to study the neurochemical effects induced by huprine X. The results show that, in a dose dependent manner, huprine X facilitates learning and memory in the Morris water maze and improves some indicators of emotionality without inducing adverse effects, affecting motor activity nor anxiety-like behaviours, as measured in the open-field and corner tests. Moreover activation of downstream PKC/MAPK signaling pathways may underly these behavioural effects as well as the stimulation of the non-amyloidogenic processing of APP. Results obtained herein using a sample of aged animals strongly suggest that huprine X constitutes a promising therapeutic agent for the treatment of cholinergic dysfunction underlying aging and/or dementias. © 2010 Elsevier Inc.
Original languageEnglish
Pages (from-to)485-493
JournalPharmacology Biochemistry and Behavior
Volume95
DOIs
Publication statusPublished - 1 Jan 2010

Keywords

  • Acetylcholinesterase inhibitors
  • Aging
  • Amyloid precursor protein (APP)
  • Huprine X
  • Learning and memory activation
  • Mitogen activated protein kinase (MAPK)
  • Protein kinase Cα (PKCα)

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