Cellular inclusions containing ubiquitin and -synuclein were observed in PC12 cells treated with metamphetamine (MA). To study the possible involvement of -arrestin in inclusion formation, we treated PC12 cells with MA for different times and analyzed the ubiquitin proteosome pathway (UPP). We found that -arrestin is ubiquitinated in the MAtreated PC12 cell line. The involvement of -arrestin in UPP was further supported by electron microscopy and by confocal microscopy, which documented the presence of -arrestin in these Lewy body-like inclusions. Our experiments reveal an interesting and previously unappreciated connection between -arrestin and ubiquitination and suggest that -arrestin could be involved in the development of the inclusion bodies.