Biochemical and histochemical studies on the effects of imipramine-like drugs and (+)-amphetamine on central and peripheral catecholamine neurons.

Abstract

AbstractRats were depleted of tissue monoamines by reserpine treatment and were then treated with a monoamine‐oxidase inhibitor (nialamide). Subsequent injection of l‐dopa caused accumulation of dopamine (DA) and noradrenaline (NA) in brain and heart, as well as restoration of the specific histochemical catecholamine (CA) fluorescence in DA and NA nerve fibres. CA accumulation and fluorescence restoration in central and peripheral NA fibres could be largely prevented by the anti‐depressive agents desipramine and protriptyline and — in peripheral tissues only — Lu 3–010. No effect on DA fibres was observed. In‐vitro studies on tissue slices showed a blocking action of these drugs, when added to the medium, on amine uptake by central and peripheral NA fibres, but no effect on amine uptake by DA fibres. When administered to the animals before the in‐vitro experiment, desipramine was active on both central and peripheral NA fibres, Lu 3–010 on peripheral NA fibres only. In similar in‐vivo experiments (+)‐amphetamine was found to largely prevent NA accumulation, to lower the ratio of DA to its metabolite 3‐methoxytyramine, and to largely prevent the restoration of CA fluorescence in both NA and DA fibres. In‐vitro studies showed that (+)‐amphetamine was able to block amine uptake by both NA and DA fibres. The cortical NA fibres were particularly sensitive to (+)‐amphetamine, in vivo and in vitro. — In rats pretreated with nialamide only, (+)‐amphetamine promoted the accumulation of O‐methylated basic CA metabolites and reduced specific fluorescence in central non‐terminal CA axons.It is concluded that desipramine and protriptyline are able to block the reserpine‐resistant amine‐ concentrating mechanism of central and peripheral NA, but not DA fibres, whereas (+)‐amphet‐ amine appears to cause release of amines from extragranular locations within both NA and DA fibres.