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

• Published in: Pharmacology, biochemistry and behavior Vol. 95; no. 4; p. 485
• Main Authors: Ratia, M, Giménez-Llort, L, Camps, P, Muñoz-Torrero, D, Clos, M V, Badia, A
• Format: Journal Article
• Language: English
• Published: United States 01-06-2010
• Subjects: ADAM Proteins - metabolism; ADAM10 Protein; ADAM17 Protein; Aging; Aminoquinolines - administration & dosage; Aminoquinolines - adverse effects; Aminoquinolines - pharmacology; Aminoquinolines - therapeutic use; Amyloid beta-Protein Precursor - metabolism; Amyloid Precursor Protein Secretases - metabolism; Animals; Behavior, Animal - drug effects; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Cholinesterase Inhibitors - administration & dosage; Cholinesterase Inhibitors - adverse effects; Cholinesterase Inhibitors - pharmacology; Cholinesterase Inhibitors - therapeutic use; Dose-Response Relationship, Drug; Heterocyclic Compounds, 4 or More Rings - administration & dosage; Heterocyclic Compounds, 4 or More Rings - adverse effects; Heterocyclic Compounds, 4 or More Rings - pharmacology; Heterocyclic Compounds, 4 or More Rings - therapeutic use; Hippocampus - drug effects; Hippocampus - metabolism; Learning - drug effects; Male; Membrane Proteins - metabolism; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases - metabolism; Motor Activity - drug effects; Protein Kinase C-alpha - metabolism; Protein Transport - drug effects; Random Allocation; Signal Transduction - drug effects; Time Factors
• ISSN: 1873-5177
• DOI: 10.1016/j.pbb.2010.03.013

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 alpha-secretase (ADAM10 and TACE/ADAM17) related to amyloid precursor protein (APP) processing remain to be established. In the present work, 12 month old 126/SvxC57b/6 male mice which received chronic i.p. treatment with either saline, huprine X (0.04 micromol kg(-1) or huprine X (0.12 micromol kg(-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.