Early spatial memory deficit induced by 2,5-hexanedione in the rat

• Published in: Toxicology letters Vol. 128; no. 1; pp. 107 - 115
• Main Authors: Carney, R, Dardis, C, Cullen, W.K, Felipo, V, Anwyl, R, Rowan, M.J
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Shannon Elsevier Ireland Ltd 10-03-2002; Amsterdam Elsevier Science
• Subjects: 2,5-Hexanedione; Animals; Behavior, Animal - drug effects; Behavior, Animal - physiology; Biological and medical sciences; Body Weight - drug effects; Cognition; Cognition - drug effects; Cognition - physiology; Drinking - drug effects; General aspects. Methods; Hexanones - adverse effects; Hexanones - pharmacology; Male; Maze Learning - drug effects; Maze Learning - physiology; Medical sciences; Memory; Memory Disorders - chemically induced; Motor activity; n-Hexane metabolite; Pilot Projects; Rats; Rats, Wistar; Spatial Behavior - drug effects; Spatial Behavior - physiology; Spatial navigation; Toxicology; Motor activity; Memory; 2,5-HD, 2,5-hexanedione; Spatial navigation; n-Hexane metabolite; Cognition; 2,5-Hexanedione
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/S0378-4274(01)00538-0

2,5-Hexanedione (2,5-HD), the major common neurotoxic metabolite of
n-hexane and methyl
n-butyl ketone, causes a delayed neuropathy with associated sensorimotor impairments. The question arises as to whether specific cognitive deficits occur even prior to changes in sensorimotor ability. The present experiments examined the effects of 2,5-HD on spatial navigation of rats in a water maze at levels/times that did not affect spontaneous exploratory motor activity in an open field holeboard apparatus. Exposure to 1% 2,5-HD in the drinking water for 2 weeks did not significantly affect escape learning, as measured by latency to find a hidden platform. However, 2,5-HD treated animals were impaired in the use of a spatial strategy during a recall test. A similar impairment in spatial memory was observed after i.p. injection of 500 mg/kg/day 2,5-HD for 4 days, in the absence of significant changes in sensorimotor ability or weight loss. Thus 2,5-HD may mediate some of the cognitive effects of hexacarbons and these changes can occur prior to the development of motor symptoms.