Amphetamines induce ubiquitin- positive inclusions within striatal cells

Abstract The present study explores whether effects induced by amphetamine derivatives on striatal GABA cells might be connected with effects on dopamine (DA) metabolism. Methamphetamine (METH) and 3,4-methylene-dioxymethamphetamine (MDMA, “ecstasy”) were adminis-tered to C57Black mice following a dosage regimen in which various doses of both drugs were injected i.p. at 2-h intervals. Neuronal inclusions produced under these experimental con-ditions were examined under electron microscopy. Drugs reducing DA availability prevented inclusion formation; conversely we observed that increasing DA synthesis or impairing physiological DA degradation enhanced the num-ber of inclusions. The present study indicates that the pres-ence of extracellular striatal DA is essential for the produc-tion of subcellular alterations induced by amphetamin