Environmental factors during early developmental period influence psychobehavioral abnormalities in adult PACAP-deficient mice

• Published in: Behavioural brain research Vol. 209; no. 2; pp. 274 - 280
• Main Authors: Ishihama, Toshihiro, Ago, Yukio, Shintani, Norihito, Hashimoto, Hitoshi, Baba, Akemichi, Takuma, Kazuhiro, Matsuda, Toshio
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 19.06.2010; Elsevier
• Subjects: Age Factors; Age-dependency; Aggression - physiology; Analysis of Variance; Animals; Anxiety - genetics; Behavior, Animal - physiology; Behavioral psychophysiology; Biological and medical sciences; Enriched environment; Exploratory Behavior - physiology; Fundamental and applied biological sciences. Psychology; Gene-environment interaction; Mice; Mice, Knockout; Motor Activity - genetics; PACAP; Pituitary Adenylate Cyclase-Activating Polypeptide - genetics; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychomotor abnormalities; Sensory Gating - genetics; Social Behavior; Social Environment; Social Isolation; Swimming; Age-dependency; PACAP; Psychomotor abnormalities; Social isolation; Gene-environment interaction; Enriched environment; Rodentia; Environmental factor; Psychomotricity; Stimulating environment; Neuropeptide; Vertebrata; Mammalia; Genotype environment interaction; Mouse; Adult animal; Dependence; Development; Early; Age; Pituitary adenylate cyclase activating peptide
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2010.02.009

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.