Specific tricyclic antidepressant binding sites in rat brain characterised by high-affinity 3H-imipramine binding

The specific binding of 3H-imipramine to various brain regions of the rat is of high affinity (Kd = 4.0 nM), rapid and reversible. It was inhibited by tricyclic antidepressants at nanomolar concentrations and by atypical antidepressants at micromolar concentrations. The binding does not seem to be directly related to known neurotransmitter receptor systems. Specific 3H-imipramine binding sites were unequally distributed between the various brain regions and undetectable in the heart and vas deferens. Rats chronically treated with desipramine for three weeks had significantly less specific 3H-imipramine binding sites in the cortex than did control animals. It is concluded that these 3H-imipramine binding sites may be important in the study of depression and of the mechanism of action of antidepressant drugs.