Behavioural characteristics and gene expression in the hyperactive wiggling (Wig) rat.
Recently, congenic wiggling (Wig) rats were described as a good model for attention-deficit hyperactivity disorder; 12- to 14-week-old animals demonstrated hyperactivity, impulsive behaviour and an impaired working memory. Here, we show that 4- to 5-week-old Wig rats displayed significantly greater spontaneous motor activity than control rats during a period of darkness. Subcutaneous injection of 4 mg/kg methamphetamine exacerbated hyperactivity, the reverse of its effect in rats with neonatally induced 6-hydroxydopamine lesions. Immunohistochemistry showed low levels of tyrosine hydroxylase in the ventral midbrain, similar to 6-hydroxydopamine-treated rats. In cDNA macroarrays, 4-week-old Wig rats showed increased expression of the adenosine A2a receptor in the dorsal striatum, macrophage migration inhibitory factor in the frontal cortex, ventral striatum and midbrain, and calbindin 2 in the dorsal and ventral midbrain. Expression of the gamma-aminobutyric acid (GABA) transporter and sterol carrier protein 2 genes was reduced in all regions. Dopamine transporter gene expression was increased in the dorsal midbrain but decreased in the ventral midbrain, a pattern distinct from that induced by 6-hydroxydopamine. Although abnormal development of dopaminergic neurons may underlie motor hyperactivity, other mechanisms may control responsiveness to methamphetamine. Wig rats may provide a model of attention-deficit hyperactivity disorder in which treatment with psychostimulants accelerate the hyperactivity.
Masuo
Yoshinori
Y
Human Stress Signal Research Center, National Institute of Advanced Industrial Science and Technology, Tsukuba West, 16-1 Onogawa, Tsukuba 305-8569, Japan. y-masuo@aist.go.jp
Ishido
Masami
M
Morita
Masatoshi
M
Sawa
Hirofumi
H
Nagashima
Kazuo
K
Niki
Etsuo
E
D018663:Adrenergic Agents / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D020296:Animals, Congenic; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology; D050485:GABA Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology*; D020869:Gene Expression Profiling / Q000379:methods; D006948:Hyperkinesis / Q000378:metabolism* / Q000503:physiopathology*; D008636:Mesencephalon / Q000378:metabolism; D008694:Methamphetamine / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D016627:Oxidopamine / Q000494:pharmacology; D051381:Rats; D043705:Receptor, Adenosine A2A / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D005680:gamma-Aminobutyric Acid
D018663:Adrenergic Agents; D002352:Carrier Proteins; D000697:Central Nervous System Stimulants; D050485:GABA Plasma Membrane Transport Proteins; D043705:Receptor, Adenosine A2A; C072087:sterol carrier proteins; D008694:Methamphetamine; D005680:gamma-Aminobutyric Acid; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase