Chronic antidepressant treatment increases enkephalin levels in n. accumbens and striatum of the rat.

Chronic (21 consecutive days) and not acute administration of typical (clomipramine, desipramine, amitriptyline) or atypical (iprindole, nomifensin) antidepressant drugs was found to provoke a selective increase in [Met5]enkephalin-like immunoreactivity ([Met5]ELI) in striatum and nucleus accumbens of rat brain. In parallel experiments, following chronic treatment with clomipramine, iprindole and nomifensin striatal [Leu5]enkephalin-like immunoreactivity ([Leu5]ELI) was also significantly enhanced. No variations in enzymatic activity of either enkephalinase or aminopeptidase were detected when assayed in several brain parts of animals chronically treated with antidepressants. Elevation of ELI in discrete regions of the brain might play a part in the mechanism of action of these centrally acting agents.