Intraneuronal Site of Action for Imipramine in Rat Striatal Slices

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Abstract
The uptake of 3H-labeled imipramine ([3H]IMI), an antidepressant, in rat corpus striatum slices is temperature-dependent. The accumulation is saturable and 2 apparent Km were found: 2.2 .times. 10-8 and 3.5 .times. 10-7 M. Once incorporated, the labeled drug was released from superfused slices by K+ (55 mM) depolarization in the presence of calcium ions. Imipramine was studied for its ability to induce the release of [3H]dopamine ([3H]DA) which had been previously accumulated by striatal slices. Striatal slices superfused during 1 or 6 min with imipramine (10-6-10-4 M) release substantial amounts of radioactive dopamine, independently of the presence of Ca2+ in the medium. This release is completely abolished after reserpine pretreatment. Apparently imipramine enters the dopaminergic storage vesicles and displaces dopamine. An intraneuronal mechanism of action for imipramine is discussed.