Artefactual inhibition of dopamine uptake by psychotropic drugs on striatal synaptosomal preparation

On striatal synaptosomal preparations, using a double labelling test, numerous antidepressant drugs demonstrated an inhibitory effect on [³H]DA uptake at the same high concentrations producing a [¹⁴C]DA release. This releasing effect was also shared by non-antidepressant agents and was observed on synaptosomes preloaded with [³H]5HT. The imipramine-induced release of DA was not modified by increasing concentration of K⁺, by decreasing concentration of Na⁺, by deleting Ca²⁺ from the incubation medium, or by blocking the catecholamine uptake systems with nomifensine or cocaine. The imipramine effect was reversible and was possibly initiated by a transient physico-chemical modification of the synaptosomal membrane. It was concluded that the DA uptake carrier is probably not involved in the effect of these drugs.