A neurobehavioral model of 2,5-hexanedione-induced neuropathy.
Although hexacarbons have been extensively studied as models of dying-back axonal degeneration, there has been little neurobehavioral investigation of these compounds. We have exposed Sprague-Dawley rats to 0.5% 2,5-hexanedione (2,5-HD), and followed neurobehavioral deficits continuously in the same animals throughout the disease course. A quantitative functionally-oriented behavioral battery consisted of four tests of simple-reflexive behaviors and four of more-complex behaviors. Onset of behavioral deficits appeared after four dosage weeks. More-complex behaviors became positive earliest; hindlimb dysfunction preceded forelimb signs. The pattern of neurobehavioral symptoms paralleled deficits found by others with acrylamide intoxication. This indicates: (1) the effectiveness of neurobehavioral methods in evaluating chemically dissimilar agents causing dying-back and (2) the ability of different functionally-oriented behavioral methods to reach similar conclusions. Further, the results indicate the added sensitivity in detecting disease using quantitative methods.
D000818:Animals; D001369:Axons / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D006588:Hexanones / Q000633:toxicity*; D007659:Ketones / Q000633:toxicity*; D009043:Motor Activity / Q000187:drug effects; D009048:Motor Skills / Q000187:drug effects; D009410:Nerve Degeneration / Q000187:drug effects; D009420:Nervous System / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D012018:Reflex / Q000187:drug effects
D006588:Hexanones; D007659:Ketones; C011269:2,5-hexanedione