The effect of pyridostigmine administration on the expression of pro-opiomelanocortin-derived peptides in motoneurones

Adult male mice were treated with the reversible acetylcholinesterase inhibitor pyridostigmine bromide and ifs effect on the expression of beta-endorphin and alpha-melanotropin immunoreactivity in motoneurones was examined in the cervical and lumbar spinal cord. Administration of a single dose of either 0.4 mu moles/kg or 2.0 mu moles/kg body weight caused a significant in crease in the incidence of beta-endorphin and alpha-melanotropin-immunoreactive motoneurones at 3h after the injection, in both the cervical and lumbar regions of the spinal cord. The immunoreactivity remained elevated for at least 5 days. There was a significantly higher increase in both beta-endorphin and alpha-melanotropin immunoreactive neurones at 3h after the higher dose compared to the lower dose, in both regions of the spinal cord. Repeated administration of a dose of 0.4 mu moles/kg once a day for three weeks caused increases in immunoreactive motoneurones in both regions. in the cervical region the increases were maintained for at least two weeks after the treatment was discontinued but in the lumbar region the levels had returned to normal by one week. A further dose of the drug administered at two weeks after the treatment period caused a significantly greater increase in the lumbar spinal cord than the same dose in untreated mice, indicating that a sensitization of the motoneurones had occurred. The effect of this drug on peptide expression in motoneurones may be secondary to its action to inhibit acetylcholinesterase at the neuromuscular junction. (C) 1998 Intox Press, Inc.