Protective effects of minocycline on the reduction of dopamine transporters in the striatum after administration of methamphetamine: a positron emission tomography study in conscious monkeys.
BACKGROUND
Positron emission tomography (PET) studies of methamphetamine (METH) abusers suggest that psychotic symptoms of METH abusers may be attributable to the reduction of dopamine transporters (DAT) in the human brain. However, there are currently no particular pharmacological treatments for the wide range of symptoms associated with METH abuse.


METHODS
Using a PET study in conscious monkeys, we investigated whether the second generation antibiotic minocycline could protect against the reduction of DAT in monkeys treated with METH (2 mg/kg x 3, 3-hour intervals).


RESULTS
Pretreatment and subsequent administration of minocycline significantly attenuated the reduction of DAT in the striatum of monkeys treated with METH. Furthermore, posttreatment and subsequent administration of minocycline also significantly attenuated the reduction of DAT. In contrast, repeated administration of minocycline alone did not alter the density of DAT in the striatum of monkeys treated with METH.


CONCLUSIONS
Our findings suggest that minocycline protects against METH-induced neurotoxicity in the monkey brain. Therefore, minocycline is likely to be a promising therapeutic agent for the treatment of several symptoms associated with METH use in humans.
Hashimoto
Kenji
K
Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba. hashimoto@faculty.chiba-u.jp
Tsukada
Hideo
H
Nishiyama
Shingo
S
Fukumoto
Dai
D
Kakiuchi
Takeharu
T
Iyo
Masaomi
M
D000818:Animals; D001931:Brain Mapping; D003243:Consciousness; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D008253:Macaca mulatta; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage*; D008911:Minocycline / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D049268:Positron-Emission Tomography; D013997:Time Factors
D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D018696:Neuroprotective Agents; D008694:Methamphetamine; D008911:Minocycline