Irradiation in adulthood as a new model of schizophrenia.
BACKGROUND
Epidemiological studies suggest that radiation exposure may be a potential risk factor for schizophrenia in adult humans. Here, we investigated whether adult irradiation in rats caused behavioral abnormalities relevant to schizophrenia.


RESULTS
A total dose of 15-Gy irradiation in six fractionations during 3 weeks was exposed to the forebrain including the subventricular zone (SVZ) and subgranular zone (SGZ) with male rats in the prone position. Behavioral, immunohistochemical, and neurochemical studies were performed three months after fractionated ionizing irradiation. Three months after fractionated ionizing irradiation, the total numbers of BrdU-positive cells in both the SVZ and SGZ zones of irradiated rats were significantly lower than those of control (sham-irradiated) rats. Hyperactivity after administration of the dopaminergic agonist methamphetamine, but not the N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine, was significantly enhanced in the irradiated rats although spontaneous locomotion in the irradiated rats was significantly lower than that of controls. Behavioral abnormalities including auditory sensory gating deficits, social interaction deficits, and working memory deficits were observed in the irradiated rats.


CONCLUSIONS
The present study suggests that irradiation in adulthood caused behavioral abnormalities relevant to schizophrenia, and that reduction of adult neurogenesis by irradiation may be associated with schizophrenia-like behaviors in rats.
Iwata
Yasuhide
Y
Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Shizuoka, Japan. iwata@hama-med.ac.jp
Suzuki
Katsuaki
K
Wakuda
Tomoyasu
T
Seki
Norihito
N
Thanseem
Ismail
I
Matsuzaki
Hideo
H
Mamiya
Takayoshi
T
Ueki
Takatoshi
T
Mikawa
Sumiko
S
Sasaki
Takeshi
T
Suda
Shiro
S
Yamamoto
Shigeyuki
S
Tsuchiya
Kenji J
KJ
Sugihara
Genichi
G
Nakamura
Kazuhiko
K
Sato
Kohji
K
Takei
Nori
N
Hashimoto
Kenji
K
Mori
Norio
N
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D018782:Maze Learning; D016548:Prosencephalon / Q000378:metabolism / Q000528:radiation effects; D011839:Radiation, Ionizing; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle; D012559:Schizophrenia / Q000209:etiology*; D012919:Social Behavior
D000596:Amino Acids; D015102:3,4-Dihydroxyphenylacetic Acid; D004298:Dopamine