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Pentyl‐4‐yn‐valproic acid enhances both spatial and avoidance learning and attenuates age‐related NCAM‐mediated neuroplastic decline within the rat medial temporal lobe
Author(s) -
Murphy Keith J.,
Fox Gerard B.,
Foley Andrew G.,
Gallagher Helen C.,
O'Connell Alan,
Griffin AnneMarie,
Nau Heinz,
Regan Ciaran M.
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00411.x
Subject(s) - neural cell adhesion molecule , dentate gyrus , neuroplasticity , memory consolidation , valproic acid , neuroscience , hippocampus , water maze , radial arm maze , synaptic plasticity , psychology , piriform cortex , pharmacology , chemistry , medicine , cognition , epilepsy , biochemistry , working memory , receptor , cell adhesion , cell
2‐ N ‐Pentyl‐4‐pentynoic acid [pentyl‐4‐yn‐valproic acid (VPA)] is an analogue of valproic acid that induces neuritogenesis and increases neural cell adhesion molecule (NCAM) prevalence in cultured neural cells. As memory consolidation involves synapse growth, aided by cell adhesion molecule function, we determined whether or not pentyl‐4‐yn‐VPA had cognition‐enhancing properties. Pentyl‐4‐yn‐VPA (16–85 mg/kg) significantly improved water maze learning and task retention when given prior to each training session. Acute administration of pentyl‐4‐yn‐VPA also influenced memory consolidation processes as, when given at 3 h post‐passive avoidance training, the amnesia induced by scopolamine given 6 h post‐training was prevented in a dose‐dependent manner. Chronic administration of pentyl‐4‐yn‐VPA (16.8 or 50.4 mg/kg) also significantly reduced escape latencies in the water maze task, 24 h following the last drug administration. This improved spatial learning was accompanied by enhanced neuroplasticity as the expression of NCAM polysialylated neurons in the infragranular zone of the dentate gyrus and in layer II of the perirhinal and piriform cortex was increased significantly following chronic drug treatment. The cognition‐enhancing qualities of pentyl‐4‐yn‐VPA, combined with its ability to attenuate the age‐related loss of the NCAM polysialylation state, suggest that it may effectively slow the onset of cognitive decline.