Serotonergic drugs, benzodiazepines and baclofen block muscimol-induced myoclonic jerks in a strain of mice.
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.
D006916:5-Hydroxytryptophan / Q000627:therapeutic use; D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use*; D001418:Baclofen / Q000627:therapeutic use*; D001569:Benzodiazepines; D008297:Male; D051379:Mice; D009118:Muscimol / Q000037:antagonists & inhibitors*; D009207:Myoclonus / Q000139:chemically induced / Q000188:drug therapy*; D010080:Oxazoles / Q000037:antagonists & inhibitors*; D010879:Piperazines / Q000627:therapeutic use; D011719:Pyrazines / Q000627:therapeutic use; D011956:Receptors, Cell Surface / Q000187:drug effects; D011963:Receptors, GABA-A; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000627:therapeutic use*
D014151:Anti-Anxiety Agents; D010080:Oxazoles; D010879:Piperazines; D011719:Pyrazines; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D011985:Receptors, Serotonin; D001569:Benzodiazepines; D009118:Muscimol; D012701:Serotonin; C014896:6-chloro-2-(1-piperazinyl)pyrazine; D006916:5-Hydroxytryptophan; D001418:Baclofen