The effects of 2,4-dithiobiuret on sensory and motor function.
2,4-Dithiobiuret (DTB) exposure causes a delayed onset muscle weakness in rats that has been attributed to depressed neuromuscular transmission. The present study compares the effects of DTB on both sensory and motor function in rats. Adult male Long-Evans hooded rats were exposed to saline, 0.25, 0.5, or 1.0 mg/kg/day DTB, ip, for 5 consecutive days (Days 1-5). Body weights were monitored throughout the experiment. Motor activity was measured for 1 hr in figure-eight mazes on Days 0, 6, 13, and 27. Forelimb and hindlimb grip strength were assessed on Days 6, 13, and 27. Auditory thresholds were determined for 5- and 40-kHz tones using reflex modification of the startle response on Days 0, 7, 14, and 28. Visual function was examined on Day 6 in animals exposed at 0.5 mg/kg/day using flash- and pattern-elicited visual evoked potentials (FEPs and PEPs, respectively). Thermal sensitivity was measured using the hot plate procedure. All motor endpoints were decreased in a dosage- and time-dependent manner; the higher the dosage the longer the effects lasted. There were no effects on any measure of sensory function with the exception of peak N2 of the FEP. Both the amplitude and latency of FEP N2 were altered by DTB exposure. Decreases in body weight were maximal on Day 9 at 1.0 mg/kg/day (20% from control), but recovered by Day 22. Motor activity was suppressed on Day 6 only, whereas grip strength measures were decreased on both Days 6 and 13. Auditory thresholds were not significantly altered; however, baseline startle amplitude was decreased at the highest dosage on Days 7 and 14, but recovered by Day 28. Hot plate latencies were not altered by DTB treatment. These data demonstrate that DTB produces a reversible impairment of motor function, without altering auditory, thermal, or pattern visual function. FEP N2, which is thought to arise from activity generated in the superficial layers of visual cortex, was diminished by DTB treatment, indicating that DTB can alter the function of the CNS, although effects on the motor system are more pronounced.
Crofton
K M
KM
Neurotoxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
Dean
K F
KF
Hamrick
R C
RC
Boyes
W K
WK
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects; D005071:Evoked Potentials / Q000187:drug effects; D005074:Evoked Potentials, Visual / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009046:Motor Neurons / Q000187:drug effects*; D009475:Neurons, Afferent / Q000187:drug effects*; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D012018:Reflex / Q000187:drug effects; D013216:Reflex, Startle / Q000187:drug effects; D012684:Sensory Thresholds / Q000187:drug effects; D013890:Thiourea / Q000031:analogs & derivatives* / Q000633:toxicity
D013890:Thiourea; C007540:2,4-dithiobiuret