A neurotoxic dose of methamphetamine induces gene expression of Homer 1a, but not Homer 1b or 1c, in the striatum and nucleus accumbens.
Homer proteins, which regulate the signaling pathway of metabotropic glutamate receptors, may contribute to the glutamatergic modulation of dopamine neurons in the basal ganglia. This study examined whether the induction of Homer 1 genes is or not associated with the methamphetamine-induced dopaminergic neurotoxicity in the discrete brain regions of rats. Basal levels of Homer 1a and 1c mRNAs in the forebrain regions were higher than those in the substantia nigra, whereas Homer 1b mRNA levels were higher in the substantia nigra than those in the forebrain regions examined. A neurotoxic dose (40 mg/kg, i.p.) of methamphetamine increased the mRNA and protein levels of Homer 1a in the striatum and nucleus accumbens, but not in the medial prefrontal cortex or the substantia nigra. Both Homer 1b and 1c mRNAs were not affected in any brain regions examined. These results suggest that the induction of Homer 1a gene may be involved at least in part in the methamphetamine-induced dopaminergic neurotoxicity, possibly through the glutamate-dopaminergic interaction.
Hashimoto
Kijiro
K
Center for Emotional and Behavioral Disorder, National Hospital Organization Hizen Psychiatric Center, Kanzaki, Saga 842-0192, Japan.
Nakahara
Tatsuo
T
Yamada
Hidetaka
H
Hirano
Makoto
M
Kuroki
Toshihide
T
Kanba
Shigenobu
S
D000661:Amphetamine / Q000633:toxicity*; D019969:Amphetamine-Related Disorders / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000633:toxicity; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D018698:Glutamic Acid / Q000378:metabolism; D000072233:Homer Scaffolding Proteins; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D009498:Neurotoxins / Q000633:toxicity; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D002352:Carrier Proteins; D018765:Dopamine Uptake Inhibitors; D000072233:Homer Scaffolding Proteins; D009498:Neurotoxins; D012333:RNA, Messenger; D018698:Glutamic Acid; D000661:Amphetamine; D004298:Dopamine