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


OBJECTIVE
This study was undertaken to examine the effects of SFN on behavioral changes and dopaminergic neurotoxicity in mice exposed to METH.


METHODS
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.


RESULTS
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.


CONCLUSIONS
It is therefore likely that SFN can be a useful drug for the treatment of signs associated with METH abuse in humans.
Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 1-8-1 Inohana, Chiba 260-8670, Japan.
Hongxian
H
Chen
Jin
J
Wu
Jichun
J
Zhang
Yuko
Y
Fujita
Tamaki
T
Ishima
Masaomi
M
Iyo
Kenji
K
Hashimoto
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D017879:Isothiocyanates; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000517:prevention & control*; D013454:Sulfoxides; D013861:Thiocyanates / Q000008:administration & dosage / Q000494:pharmacology*
D000975:Antioxidants; D017879:Isothiocyanates; D018696:Neuroprotective Agents; D013454:Sulfoxides; D013861:Thiocyanates; D015102:3,4-Dihydroxyphenylacetic Acid; D008694:Methamphetamine; C016766:sulforaphane; D004298:Dopamine