Environmental factors during early developmental period influence psychobehavioral abnormalities in adult PACAP-deficient mice.
Mice lacking the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) (PACAP(-/-)) display behavioral abnormalities, and genetic variants of the genes encoding PACAP are associated with schizophrenia. Clinical studies show that environmental factors, besides genetic factors, play a key role in etiology of many psychiatric disorders. This study examined the effects of environmental factors such as short-term social isolation and an enriched environment on behavioral abnormalities of PACAP(-/-) mice. Rearing in isolation for 2-weeks from 4-weeks old induced hyperlocomotion and aggressive behaviors in the PACAP(-/-) mice without affecting the behavioral performance of the wild-type controls. Adult PACAP(-/-) mice showed not only hyperactivity, jumping behavior, and depression-like behavior, but also decreased social interaction. These abnormal behaviors were improved by rearing for 4-weeks in an early enriched environment (from 4-weeks old), although the deficits of prepulse inhibition (PPI) were not influenced by the enriched condition. In contrast, rearing for 4-weeks in late enriched environment (from 8-weeks old) did not affect the hyperactivity and jumping behaviors in the PACAP(-/-) mice. These results suggest that abnormal behaviors except PPI deficits in PACAP(-/-) mice depend on the environmental factors during the early stages of development.
Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
Toshihiro
T
Ishihama
Yukio
Y
Ago
Norihito
N
Shintani
Hitoshi
H
Hashimoto
Akemichi
A
Baba
Kazuhiro
K
Takuma
Toshio
T
Matsuda
D000367:Age Factors; D000374:Aggression / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000235:genetics*; D001522:Behavior, Animal / Q000502:physiology; D005106:Exploratory Behavior / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000235:genetics*; D055139:Sensory Gating / Q000235:genetics; D012919:Social Behavior; D012931:Social Environment; D012934:Social Isolation; D013550:Swimming
D051219:Pituitary Adenylate Cyclase-Activating Polypeptide