Association between brain indole levels and severity of posthypoxic myoclonus in rats

We have previously reported the presence of posthypoxic, audiogenic myoclonus in rats after cardiac arrest and the ability of the 5-HT precursor, 5-HTP, to attenuate these muscle jerks. In addition, we have recently shown that 5-HT2 and 5-HT3 agonists can reduce the severity of myoclonus in these animals, suggesting a deficiency in serotonergic neurotransmission. In the present study, the levels of 5-HTP, 5-HT, and 5-HIAA were measured in seven regions of the brain in myoclonic and normal rats to identify the areas of the brain in which a serotonergic dysfunction resides. Similar to previous studies, we observed pronounced posthypoxic, audiogenic myoclonus 3 and 14 days after resuscitation from cardiac arrest, with a resolution of the abnormal movements by 45 days postarrest. HPLC measurements revealed significant changes in indole levels in the following areas of the brain: cortical 5-HIAA, striatal 5-HT, striatal 5-HIAA, hippocampal 5-HT, mesencephalic 5-HIAA, myelencephalic 5-HT, myelencephalic 5-HIAA, cerebellar 5-HTP, and cerebellar 5-HT. The changes in striatal 5-HT, cortical 5-HIAA, and mesencephalic 5-HIAA appear most relevant to the pathophysiology of posthypoxic myoclonus because regression analyses showed significant correlations between the myoclonus scores of the animals and the levels of these indoles. Based on the observed pattern of results, we postulate a dysfunction in serotonergic lateral (cortical) and far lateral (extrapyramidal) ascending pathways in posthypoxic myoclonus.