Motor activity and gene expression in rats with neonatal 6-hydroxydopamine lesions.
A rat model of a hyperkinetic disorder was used to investigate the mechanisms underlying motor hyperactivity. Rats received an intracisternal injection of 6-hydroxydopamine on post-natal day 5. At 4 weeks of age, the animals showed significant motor hyperactivity during the dark phase, which was attenuated by methamphetamine injection. Gene expression profiling was carried out in the striatum and midbrain using a DNA macroarray. In the striatum at 4 weeks, there was increased gene expression of the NMDA receptor 1 and tachykinins, and decreased expression of a GABA transporter. At 8 weeks, expression of the NMDA receptor 1 in the striatum was attenuated, with enhanced expression of the glial glutamate/aspartate transporter. In the midbrain, a number of genes, including the GABA transporter gene, showed decreased expression at 4 weeks. At 8 weeks, gene expression was augmented for the dopamine transporter, D4 receptor, and several genes encoding peptides, such as tachykinins and their receptors. These results suggest that in the striatum the neurotransmitters glutamate, GABA and tachykinin may play crucial roles in motor hyperactivity during the juvenile period. Several classes of neurotransmitters, including dopamine and peptides, may be involved in compensatory mechanisms during early adulthood. These data may prompt further neurochemical investigations in hyperkinetic disorders.
Masuo
Yoshinori
Y
Human Stress Signal Research Center, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan. y-masuo@aist.go.jp
Ishido
Masami
M
Morita
Masatoshi
M
Oka
Syuichi
S
Niki
Etsuo
E
D000818:Animals; D000831:Animals, Newborn; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D002395:Catecholamines / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000008:administration & dosage; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004195:Disease Models, Animal; D004563:Electrochemistry; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D006948:Hyperkinesis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D007150:Immunohistochemistry / Q000379:methods; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D016627:Oxidopamine; D051381:Rats; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D002395:Catecholamines; D000697:Central Nervous System Stimulants; D007473:Ion Channels; D009479:Neuropeptides; D011956:Receptors, Cell Surface; D008694:Methamphetamine; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase