ASSOCIATION BETWEEN BRAIN INDOLE LEVELS AND SEVERITY OF POSTHYPOXIC MYOCLONUS IN RATS

We have previously reported the presence of posthypoxic, audiogenic my oclonus in rats after cardiac arrest and the ability of the 5-HT precu rsor, 5-HTP, to attenuate these muscle jerks. In addition, we have rec ently shown that 5-HT2 and 5-HT3 agonists can reduce the severity of m yoclonus in these animals, suggesting a deficiency in serotonergic neu rotransmission. 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 nor mal rats to identify the areas of the brain in which a serotonergic dy sfunction resides. Similar to previous studies, we observed pronounced posthypoxic, audiogenic myoclonus 3 and 14 days after resuscitation f rom cardiac arrest, with a resolution of the abnormal movements by 45 days postarrest. HPLC measurements revealed significant changes in ind ole levels in the following areas of the brain: cortical 5-HIAA, stria tal 5-HT, striatal 5-HIAA, hippocampal 5-HT, mesencephalic 5-HIAA, mye lencephalic 5-HT, myelencephalic 5-HIAA, cerebellar 5-HTP, and cerebel lar 5-HT. The changes in striatal 5-HT, cortical 5-HIAA, and mesenceph alic 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 i ndoles. Based on the observed pattern of results, we postulate a dysfu nction in serotonergic lateral (cortical) and far lateral (extrapyrami dal) ascending pathways in posthypoxic myoclonus.