Amphetamine triggers an increase in met-enkephalin simultaneously in brain areas and immune cells.

We analyzed effects of amphetamine on proenkephalin-derived peptides in brain areas and immune cells in rats. Acute, as well as a repeated amphetamine treatment, decreased the concanavalin-A-induced lymphocyte proliferation, concomitantly with an increase of free met-enkephalin in nucleus accumbens, prefrontal cortex, spleen, thymus and splenic macrophages. Proenkephalin protein increased in prefrontal cortex, thymus (32 kDa isoform), nucleus accumbens and spleen (44 kDa isoform), while proenkephalin mRNA levels decreased in brain stem. The influence of met-ENK in key brain areas for sensitization and in immune organs is consistent with the idea that changes on met-ENK could underlie amphetamine's effects on brain and IS.