Protective effects of the antioxidant sulforaphane on behavioral changes and neurotoxicity in mice after the administration of methamphetamine

Methamphetamine (METH) is a powerfully addictive stimulant associated with serious health conditions. Accumulating evidence suggests a role of oxidative stress in METH-induced behavioral abnormalities. Sulforaphane (SFN), found in cruciferous vegetables, is a potent antioxidant. It is of interest to determine whether SFN can attenuate behavioral and neuropathological changes associated with METH exposure. This study was undertaken to examine the effects of SFN on behavioral changes and dopaminergic neurotoxicity in mice exposed to METH. The effects of SFN on acute hyperlocomotion and the development of behavioral sensitization induced by the administration of METH were examined. Levels of dopamine (DA) and its major metabolite 3,4-dihydroxyphenyl acetic acid (DOPAC) in the striatum were measured. In addition, DA transporter (DAT) immunoreactivity was also performed. Pretreatment with SFN at 1, 3, and 10 mg/kg elicited a dose-dependent attenuation of acute hyperlocomotion in mice, after a single administration of METH (3 mg/kg). The development of behavioral sensitization after repeated administrations of METH (3 mg/kg/day, once daily for 5 days) was significantly reduced by pretreatment with SFN (10 mg/kg). In addition, the lowering of DA levels and DOPAC as well as DAT immunoreactivity in the striatum, usually seen after repeated administration of METH, was significantly attenuated by both pretreatment and the subsequent administration of SFN. Furthermore, SFN significantly reduced microglial activation in the striatum after repeated exposure to METH. It is therefore likely that SFN can be a useful drug for the treatment of signs associated with METH abuse in humans.