The effect of drugs on the concentration of dopamine β-hydroxylase in the cerebrospinal fluid of rabbits

Abstract

Systemic administration of each of the drugs studied (phenoxybenzamine, yohimbine, phentolamine, nicotine, physostigmine and pentylenetetrazol) caused an increase in the dopamine β-hydroxylase activity per unit volume of cerebrospinal fluid. The increase was gradual starting within 90 min after injection of the drug and remained high for at least 3 h. At that time the dopamine β-hydroxylase levels after treatment with phenoxybenzamine and yohimbine reached values of 600% and 580%, respectively, of the control. The increase in dopamine β-hydroxylase activity upon phenoxybenzamine treatment was dose dependent. Injection of pentylenetetrazol caused an increase in dopamine β-hydroxylase to 230% of the control value. Pretreatment of rabbits with an intracisternal injection of 6-hydroxydopamine not only caused a 68% decrease in the noradrenaline content and a 69% decrease in the dopamine β-hydroxylase levels in the brain, but also led to a 52% fall in the dopamine β-hydroxylase level of the cerebrospinal fluid. Upon injection of pentylenetetrazol into rabbits pretreated with 6-hydroxydopamine, the dopamine β-hydroxylase levels in the cerebrospinal fluid only reached a mean value of 0.98 units/ml compared with 2.62 units/ ml for control rabbits injected with pentylenetetrazol; the increase in the blood level of dopamine β-hydroxylase activity was, however, unaffected. Data derived from normal and 6-hydroxydopamine pretreated rabbits revealed a fairly good correlation between dopamine β-hydroxylase levels in the cerebrospinal fluid and the brain. From these experiments it is concluded that dopamine β-hydroxylase activity in the cerebrospinal fluid is derived from central noradrenergic neurons and that drugs which increase central noradrenergic activity also increase dopamine β-hydroxylase levels in the cerebrospinal fluid. It is further suggested that determination of dopamine β-hydroxylase activity in the cerebrospinal fluid may be a sensitive and relatively easy method to assess central noradrenergic activity.