Nuclear Medicine Technology and other Health Applications Project Title: 16, Treatment and Biochemical Dissection of Parkinsonism and Allied Conditions Technical Progress in FY 1973: RX-01-03-(a) (Cont'd.) These studies (and others) were facilitated by the development of an automated ergometer, for the fast, simple, and quantitative assessment of changes of the neurological state in parkinsonism, The changes in output of work correlated with the neurological changes determined with a con- ventional scoring system. Studies on cerebrospinal fluid (CSF) showed Levodopa and dopamine to be present only after levodopa administration and not in control patients; however, effects, their levels did not correlate with dose, improvement or sideWhen L-dopa was given with pyridoxine, the level of levodopa in the CSF dropped and correlated with a loss of therapeutic efficacy. However, a more convenient biochemical marker for the effect of pyridoxine is the determination of urinary dopamine. Thus, the usefulness of CSF analyses in following the treatment of parkinsonism is questioned. Animal experiments are proposed to develop methods applicable to brain biopsies. In order to maximize the chemical information one can obtain from these biopsies a method was developed to analyze biopsy samples of brain for manganese and catecholamines, This micro-method combines nondestructive Neutron activation analysis for manganese with spectrofluoremetric determina- tion of dopa and dopamine in the same sample. Reaction of cats given 200 and 400 mg/kg (i.p.) of saline or levodopa were scored. The animals were then anesthetized for sampling the caudate, the hypothalamus, the corpus callosum, the frontal white and frontal gray cortex. Administration of levodopa was found to increase the concentration of dopa and dopamine in all areas studied. In the caudate area the level of dopamine showed a high correlation with behavioral scores. Ranking of control animals according to dopamine concentration in the caudate had a coefficient of 0.8 with their ranking by manganese concentration in this nucleus. Manganese levels in the hypothalamus appeared to correlate with those of dopamine, Upon completion of this phase of the study regional brain samples from living cats will be obtained stereotactically in preparation for studies in appropriate human subjects, In other studies on interactions between levodopa and manganese, young mice (three weeks of age) showed both higher responses to levodopa and faster turnover of manganese than adult animals, implying correlations between the two. Data obtained on newborn mice, their mothers, and mice of variowg ages, include: 1) concentration of Mn in embryonic liver is about 1/6 that of the adult and remains at that level until the 12th postpartum day; BFat day 18 liver Mn peaks to 11.8 + 2.5 ug/g dry weight (adult 3.0 pg/g) in offspring from mothers fed purina chow, in contrast to off- spring from mothers fed milk; 3) the peak persisted between days 17 and 19, followed by a slow decline to adult levels at about 5 weeks; 4) Mn-54 was not eliminated from the whole body between birth and the l8thday of life, 5) one week old mice injected with radiomanganese incorporated 0.3% of the (See Continuation Sheet) bi 19198 RX-40