Pentyl-4-yn-valproic acid reverses age-associated memory impairment in the Wistar rat.
Pentyl-4-yn-valproic acid (VPA), a cognition-enhancing agent whose mode of action has been attributed to cell adhesion molecule-mediated neuritogenesis, has been shown to enhance hippocampus-dependent spatial learning. Here, we investigated its potential to reverse age-related memory impairment that relates mainly to declarative memory. Aged spatial learning deficits in the water maze paradigm were demonstrated by swim angle analysis, the angle between axes of start-to-platform and start-to-animal position, and latency to reach a submerged platform. Chronic pentyl-4-yn-VPA administration mediated a significant improvement in both search strategy and latency to find the submerged platform in aged animals. Pentyl-4-yn-VPA also facilitated task recall in aged animals as evidenced by increased time in the target quadrant during a probe trial 3 days following the final training session. The action of pentyl-4-yn-VPA on platform latency, search strategy and task recall suggests that this agent may have great benefit in the treatment of age-dependent cognitive decline.
Foley
Andrew G
AG
Department of Pharmacology, The Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
Gallagher
Helen C
HC
Murphy
Keith J
KJ
Regan
Ciaran M
CM
D000375:Aging / Q000187:drug effects* / Q000502:physiology / Q000523:psychology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D014635:Valproic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*
C434604:pentyl-4-yn-valproic acid; D014635:Valproic Acid