Methamphetamine induces fos expression in the striatum and the substantia nigra pars reticulata in a rat model of Parkinson's disease.
In rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion in the nigrostriatal pathway, methamphetamine (3 mg/kg, i.p.) induced Fos-like immunoreactivity (FLI) not only in the striatum on the intact side but also in the substantia nigra pars reticulata (SNr) on the lesioned side. The methamphetamine-induced hyperexpression of FLI in the SNr on the lesioned side was suppressed by pretreatment with either dopamine D1 receptor antagonist SCH-23390 (0.5 mg/kg, i.p.), D2 receptor antagonist raclopride (2 mg/kg, i.p.) or N-methyl-d-aspartate receptor antagonist MK-801 (1 mg/kg, i.p.), which was concomitant with inhibition of the methamphetamine-induced rotational behavior of each antagonist. However, the hyperexpression of FLI in the SNr was not suppressed by intrastriatal grafts of fetal ventral mesencephalon which could suppress the methamphetamine-induced rotation completely. These results indicate that opposite hemispheric asymmetries in FLI are induced by methamphetamine in the striatum and the SNr in the 6-OHDA rats. It is suggested that the FLIs in the two discrete sites are activated independently by different mechanisms, and furthermore, different neuronal pathways are involved in the methamphetamine-induced rotation and Fos expression in the SNr of 6-OHDA rats.
Ishida
Y
Y
Department of Psychiatry, Miyazaki Medical College, 5200 Kihara, Kiyotake-cho, Miyazaki-gun, Miyazaki 889-1692, Japan. ishiday@post.miyazaki-med.ac.jp
Todaka
K
K
Kuwahara
I
I
Ishizuka
Y
Y
Hashiguchi
H
H
Nishimori
T
T
Mitsuyama
Y
Y
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects; D016380:Brain Tissue Transplantation; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism*; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D008636:Mesencephalon / Q000637:transplantation; D008694:Methamphetamine / Q000494:pharmacology*; D009474:Neurons / Q000737:chemistry / Q000201:enzymology; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D020891:Raclopride; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000502:physiology; D012399:Rotation; D012457:Salicylamides / Q000494:pharmacology; D013378:Substantia Nigra / Q000166:cytology / Q000378:metabolism*; D013565:Sympatholytics; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D001552:Benzazepines; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D018691:Excitatory Amino Acid Antagonists; D016760:Proto-Oncogene Proteins c-fos; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D013565:Sympatholytics; D020891:Raclopride; D008694:Methamphetamine; D016291:Dizocilpine Maleate; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase