In male Swiss mice,
muscimol produced
myoclonic jerks. A 3 mg/kg (i.p.) dose induced this response in all of the mice tested and the peak response of 73 jerks per min was observed between 27 and 45 min. Increasing the brain
serotonin levels by the administration of
5-hydroxytryptophan (80-160 mg/kg) in combination with a peripheral
decarboxylase inhibitor resulted in an inhibition of the
muscimol effect. However, in a similar experiment
l-dopa (80-160 mg/kg) was without effect. In doses of 3-10 mg/kg, the
serotonin receptor agonist MK-212 caused a dose-dependent blockade of the response of
muscimol. Of the
benzodiazepines,
clonazepam (0.1-0.3 mg/kg) was found to be several fold more potent than
diazepam (0.3-3 mg/kg) in blocking the
myoclonic jerks. While (-)-
baclofen (1-3 mg/kg) proved to be an effective antagonist of
muscimol, its (+)-isomer (5-20 mg/kg) lacked this property. Considering the fact that
5-HTP and the
benzodiazepines have been found to be beneficial in the management of clinical
myoclonus, the
muscimol-induced
myoclonus seems to be a satisfactory animal model that may prove useful for the development of new
drug treatments for this condition. Our present study indicated the possible value of
MK-212 and (-)-
baclofen in the management of clinical
myoclonus.