Inhibition of the uptake of tritiated 5-hydroxytryptamine in brain tissue

Abstract

The uptake of tritialted 5-hydroxytryptamine (5-HT) in slices of mouse brain was examined in vitro. A part of this uptake was inhibited by cocaine and was limited to concentrations of 5-HT below 3 × 10 −6 M. This had the nature of an active uptake process. The other part was linear with the 5-HT concentration and had the nature of a partitions of 5-HT between the solution and the tissue. Reserpine reduced the accumulation of 5-HT but did not influence the rate of the initial uptake, which was strongly reduced by cocaine, imipramine and tryptamine derivatives. In vitro, the tertiary tricyclic antidepressant agents imipramine and amitriptyline were more active than their secondary analogues desipramine and nortriptyline in inhibiting the uptake of 5-HT. In vivo, this difference was further accentuated, probably because the tertiary amines reach a higher brain concentration, this being shown to apply for imipramine compared with desipramine.