Central and peripheral dopamine beta hydroxylase: responses to long term treatment with monoamine oxidase inhibitors.

Abstract

Abstract The effect of long-term (3 weeks) treatment with monoamine oxidase inhibitors on dopamine beta hydroxylase (DBH) in cats was studied. The DBH was measured in blood and CSF drawn before treatment began and after 2, 8, 14, and 22 days of injections. Animals were killed after 24 days of injections, and DBH was measured in brain cortex and pons-medulla. Both clorgyline and pargyline decreased DBH activity in CSF after 22 days of treatment. These drugs decreased plasma DBH after 8 days of treatment, and the decrease persisted throughout the study. Brain DBH levels in the drug-treated animals were not significantly different from enzyme levels in saline-treated controls. The decrease in CSF DBH occurred 2 weeks after the decrease in the plasma enzyme, suggesting that CSF DBH levels do not simply reflect plasma DBH levels. The decrease in DBH in CSF was not caused by a large-scale depletion of the enzyme in brain. It is likely that the observed change in CSF DBH is due to a decrease in central noradrenergic activity, which has been demonstrated in rats. It is of interest that this change is seen only after three weeks of drug treatment, at the time when the therapeutic effects of these drugs become evident in patients.