Effects of chronic treatment with 2,5-hexanedione on several behavioral measures in rats

Abstract

Exposure to hexacarbon compounds may cause several neurotoxic effects in both animals and humans. In the present study, we subcutaneously administered, chronically for 15-50 days, 2,5-HD (a toxic metabolic ofn-hexane) to invelitigate-its effects on open-field behavior, step-down inhibitory avoidance, and shuttle avoidance. The results demonstrated that at 20 mg/kg 2,5-HD did not alter any of the behavioral tasks analyzed. On the other hand, at 200 mg/kg 2,5-HD caused significant reductions on body-weight gain (10% at 25 days of treatment and 25% at 61 days) and the general motor activity of rats treated for 15 or 30 days; treatment did not interfere with habituation to the open field. Inhibitory avoidance performance was not affected, but shuttle avoidance was significantly impaired in the high-dose, long-and short-term treated rats, probably as a consequence of the general debilitation of motor activity in treated rats.Exposure to hexacarbon compounds may cause distal axonopathy in the central and peripheral nervous systems of both humans and animals (Spencer, Schaumburg, Sabri, & Veronesi, 1980). Various studies have demonstrated that workers occupationally exposed to n-hexane present peripheral polyneuropathy (Couri & Milks, 1982; Herskowitz, Ishii, & Schaumburg, 1971). n-Hexane is metabolized to a series of metabolites, including 1hexanol, 2-hexanol, 3-hexanol, 2-hexanone, 5-hydroxy-2-hexanone, and 2,5-hexanedione (Couri & Milks, 1982;DiVicenzo, Kaplan, & Dedinas, 1976). Although the exact mechanism underlying the neurotoxic effects of hexacarbon compounds is not yet established, it has been demonstrated that the hexacarbon compound 2,5-hexanedione may cause severe toxic effects with chronic administration to animals, including severe deficits in motor and sen-