Concentration of striatal tyramine and dopamine metabolism in diabetic rats and effect of insulin administration.

Abstract

Earlier work has shown that diabetic rats possess lower concentrations of brain p-tyrosine; these animals also show a decrease in the rate of accumulation of striatal DOPA after decarboxylase inhibition and an increase in striatal binding sites for dopamine. These findings suggested that diabetic rats show a reduction in the metabolism of brain dopamine. This is an investigation of the effects of streptozotocin-induced (65 mg/kg, intracardially) diabetes on rat striatal concentrations of p-tyrosine, p-tyramine, m-tyramine, dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid. Also, the effects of insulin administration (0.5-4 IU/kg, intraperitoneally) to normal and diabetic rats were studied. The onset of diabetes or effect of insulin treatment was determined by the changes produced in blood glucose. Streptozotocin produced a significant reduction in the striatal concentration of p-tyrosine, 3,4-dihydroxyphenylacetic acid and homovanillic acid observed 7 or 14 days after injection. The treatment produced a reduction in p-tyramine and an increase in m-tyramine. Insulin administration significantly increased rat striatal p-tyrosine, p-tyramine, 3,4-dihydroxyphenylacetic acid and homovanillic acid while m-tyramine was decreased. The concentrations of p-tyrosine, dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid in the striatum of insulin-treated diabetic rats were within the range of control values. The results indicate that streptozotocin-diabetic rats possess a reduced striatal dopamine metabolism and that this is counteracted by insulin administration. These changes are probably the consequence of changes in the availability of some amino acid precursors and in tyrosine hydroxylase activity.