Y.M. and M.I. contributed equally to this study.
Behavioural characteristics and gene expression in the hyperactive wiggling (Wig) rat
Article first published online: 28 JUN 2007
European Journal of Neuroscience
Volume 25, Issue 12, pages 3659–3666, June 2007
How to Cite
Masuo, Y., Ishido, M., Morita, M., Sawa, H., Nagashima, K. and Niki, E. (2007), Behavioural characteristics and gene expression in the hyperactive wiggling (Wig) rat. European Journal of Neuroscience, 25: 3659–3666. doi: 10.1111/j.1460-9568.2007.05613.x
- Issue published online: 28 JUN 2007
- Article first published online: 28 JUN 2007
- Received 18 January 2007, revised 1 May 2007, accepted 1 May 2007
- adenosine receptor;
- attention-deficit hyperactivity disorder;
- DNA array;
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 γ-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.