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.