Myoclonus in the rat induced by p,p'-DDT and the role of altered monoamine function.
Administration of p,p'-DDT to rats produced myoclonus, but unlike previous studies in mice, this was not decreased by administration of clonazepam. Precursors of 5-hydroxytryptamine (5-HT) (L-tryptophan and L-5-HTP) reduced the intensity of myoclonus, but the 5-HT agonists, quipazine and Org 6582 did not. Antagonists of 5-HT (methergoline, methysergide and cinanserin) did not potentiate the myoclonus induced by p,p'-DDT. Drugs altering the function of dopamine and noradrenaline (apomorphine, clonidine or phenoxybenzamine) also had no effect on this myoclonus. Administration of monoamine oxidase inhibitors (MAOIs; pargyline, nialamide and tranylcypromine) markedly attenuated the myoclonus, an effect that could not be attributed to an action on any one monoamine system. No observable changes in cerebral biochemical parameters of 5-HT occurred at the onset of myoclonus, although tryptophan and 5-hydroxyindoleacetic acid (5-HIAA) in brain were increased following periods of prolonged myoclonus. Electrophysiological analysis of the myoclonus in the rat induced by p,p'-DDT revealed changes in EEG and EMG activity which suggested an origin for the myoclonus in the brainstem. Although this was similar to electrophysiological findings in some human patients with post-anoxic action myoclonus, the pharmacological studies suggest that the myoclonus induced by p,p'-DDT in the rat is not a suitable model for screening potential drugs to be used in the treatment of this disorder.
D000818:Animals; D001921:Brain / Q000503:physiopathology; D002998:Clonazepam / Q000627:therapeutic use; D003634:DDT / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000627:therapeutic use; D009207:Myoclonus / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology; D009638:Norepinephrine / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000502:physiology
D008996:Monoamine Oxidase Inhibitors; D012701:Serotonin; D002998:Clonazepam; D003634:DDT; D004298:Dopamine; D009638:Norepinephrine