Selective reserpine-resistant accumulation of catecholamines in central dopamine neurones after dopa administration

Abstract

The capacity of central monoamine neurones to form and store catecholamines (CA), following administration of DOPA, has been investigated in reserpine pretreated rats. Fluorescence histochemistry showed that there occur selective accumulations of CA in previously known dopamine (DA) nerve terminals following treatment with DOPA together with a peripheral decar☐ylase inhibitor (Ro4-4602, MK-486) of reserpine pretreated rats. These DA accumulations were readily depleted amphetamine and associated with the apperance of marked stereotyped behaviour. In vitro experiments with [ 3H]noradrenaline ([ 3H]NA) revealed that with a concentration of10 −5 M but not with 10 −7 M selective accumulation of [ 3H]NA occurs in homogenates of neostriatum from reserpine treated animals. The monoamine oxidase (MAO) activity in the neostriatum and the neocortex was not affected by reserpine pretreatment. It is suggested that the selective accumulation of CA in the DA nerve terminals in the presence of high amine concentrations could be the result of a reserpine-resistant binding of CA to the DA granules, a binding which could partly protect the store from the action of MAO. This discovery has made it possible to further characterize and trace DA terminals. Evidence has been obtained that new types of presumaby DA nerve terminals may exist in the limbic cortex, particularly in the cingulate cortex, and also in certain parts of the neocortex (frontal cortex). In addition, some of the CA terminals in the septal area may be DA nerve terminals. New types of nerve cell bodies lacking endogenous monoamine fluorescence have been mapped out in the brain, particularly in the hypothalamus and the preoptic area which can take up and decar☐ylate DOPA. These cells may contain a monommine-like compound.