New rat model for attention deficit hyperactive disorder (ADHD).
OBJECTIVE
In a strain of the Long-Evans Cinnamon (LEC) rats, we found spontaneously hyperactive animals designated as "wiggling," and established a congenic wiggling (Wig) rat by transferring the gene from the LEC to the Wistar King-Aptekman/Hokkaido (WKAH) strain. We evaluated the feasibility of the Wig rat for an animal model of human attention deficit hyperactive disorder (ADHD).


METHODS
Mode of inheritance was examined by use of linkage analyses. Motor activity, behavior, and working memory were assessed by use of electric digital counters, open field test, and Y-maze and water-maze tests.


RESULTS
The abnormal behavior, including hyperactivity, was transmitted in autosomal recessive mode. Diurnal and nocturnal motor activity of 12- to 14-week-old Wig rats was markedly higher than that of controls, and this hyperactivity was more prominent during nighttime than daytime. Ambulation in the open-field test was significantly increased in Wig rats, but rearing was decreased in Wig rats, compared with controls. Results of the Y-maze tests indicated that spontaneous alternation behavior was significantly impaired in Wig rats, although there was no difference in the total arm entries. The water-maze test could not be performed because, when exposed to water, Wig rats panicked and almost drowned.


CONCLUSIONS
Wig rats are hyperactive and have impaired working memory and impulsive behavior, as assessed by the motor activity and open-field tests and the Y-maze test, and these abnormalities are transmitted by a single gene with Mendelian pattern. Wig rats represent an excellent animal model of human ADHD.
Kamimura
E
E
Center for Experimental Plants & Animals, Hokkaido University, Sapporo, Japan.
Ueno
Y
Y
Tanaka
S
S
Sawa
H
H
Yoshioka
M
M
Ueno
K I
KI
Inoue
T
T
Li
X
X
Koyama
T
T
Ishikawa
R
R
Nagashima
K
K
D000818:Animals; D020296:Animals, Congenic; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology / Q000523:psychology; D001522:Behavior, Animal; D002940:Circadian Rhythm; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D008297:Male; D018782:Maze Learning; D008568:Memory; D009043:Motor Activity / Q000235:genetics; D009420:Nervous System / Q000473:pathology; D051381:Rats; D020332:Rats, Inbred LEC; D011922:Rats, Mutant Strains; D017208:Rats, Wistar