Acta Neuropathologica

, Volume 65, Issue 1, pp 77–84 | Cite as

Effects of dithiobiuret intoxication on motor end plates in sternocostalis and hindlimb muscles of female rats

  • S. Kemplay
Original Works


Daily dosing with 1–3 mg/kg dithiobiuret for 4–5 days causes progressive, generalised muscle weakness which is fatal in about 50% of cases on day 4 or 5. Survivors recover mobility by day 7 and appear normal, although still weak. Striking changes in the motor nerves and motor end plates can be observed before and during the development of this weakness, using the zinc iodide-osmium staining technique. The terminal internodes of intramuscular axons become densely stained: later this may extend back into the main intramuscular (i.m.) nerves, and is often followed by axonal degeneration. Many motor end plates lose their branching form and become globular, and profuse terminal sprouting develops before any nerve degeneration appears. Following axonal degeneration, collateral sprouting becomes prominent, and, within four weeks of beginning the dose regime, restores the normal appearance of the innervation.

This pattern of response was observed clearly in the whole mounts of the sternocostalis muscle: similar but less marked changes occurred in the lumbrical muscles, while in the soleus and tibialis anterior muscles, loss of end plates seemed to be a more common response.

Despite marked differences in the severity of the functional disability, the i.m. changes were similar in juvenile and adult rats.

These changes are related to previous electrophysiological findings on the possible mechanism of action of dithiobiuret.

Key words

2,4-dithiobiuret Rat Motor end plate 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Akert K, Sandri C (1968) An electron-microscopic study of zinc iodide-osmium impregnation of neurons. I. Staining of synaptic vesicles at cholinergic junctions. Brain Res 7:286–295Google Scholar
  2. Astwood EB, Hughes AM, Lubin M, Vander Laan WP, Adams RD (1945) Reversible paralysis of motor function in rats from the chronic administration of dithiobiuret. Science 102:196–197Google Scholar
  3. Atchison WD, Peterson RE (1981) Potential neuromuscular toxicity of 2,4-dithiobiuret in the rat. Toxicol Appl Pharmacol 57:63–68Google Scholar
  4. Atchison WD, Lalley PM, Cassens RG, Peterson RE (1981a) Depression of neuromuscular function in the rat by chronic 2,4-dithiobiuret treatment. Neurotoxicology 2:329–346Google Scholar
  5. Atchison WD, Yang KH, Peterson RE (1981b) Dithiobiuret toxicity in the rat: evidence for latency and cumulative dose thresholds. Toxicol Appl Pharmacol 61:166–171Google Scholar
  6. Atchison WD, Dickins J, Peterson RE (1982a) Age dependence of dithiobiuret neurotoxicity in male and female rats. Neurotoxicology 3:233–242Google Scholar
  7. Atchison WD, Mellon WS, Lalley PM, Peterson RE (1982b) Dithiobiuret-induced muscle weakness in rats: evidence for a prejunctional effect. Neurotoxicology 3:44–54Google Scholar
  8. Barker D, Ip MC (1966) Sprouting and degeneration of mammalian motor axons in normal and de-afferented skeletal muscle. Proc R Soc Lond [Biol] 163:538–554Google Scholar
  9. Duchen LW, Strich S (1968) The effects of botulinum toxin on the pattern of innervation of skeletal muscle in the mouse. Q J Exp Physiol 53:84–89Google Scholar
  10. Ironton R, Brown MC, Holland RL (1979) Stimuli to intramuscular nerve growth. Brain Res 150:351–354Google Scholar
  11. Porter WR, Williams KD, Peterson RE (1982) Synthesis, purification and stability in solution of dithiobiuret-2,4-35S. J Lab Comp Radiopharmaceut 19:881–889Google Scholar
  12. Simonati A, Cavanagh JB (1984) Changes in terminal sprout formation in rat sternocostalis muscle during chronic intoxication with 2,5-hexanedione. Muscle Nerve (in press)Google Scholar

Copyright information

© Springer-Verlag 1984

Authors and Affiliations

  • S. Kemplay
    • 1
  1. 1.Institute of NeurologyLondonUK

Personalised recommendations