Neonatal phencyclidine treatment in mice induces behavioral, histological and neurochemical abnormalities in adulthood.
We investigated the involvement of glutamic acid in neural development by injecting phencyclidine (PCP) into neonatal ICR mice. Neonatal mice were injected with PCP at 10 mg/kg or saline on postnatal days 7, 9 and 11, and their behavioral, anatomical and neurochemical changes were analyzed in adulthood. PCP-treated mice exhibited an increase in PCP-induced hyperactivity and impairments of spatial working memory and social interaction behavior. The impairment of social interaction behavior was significantly reversed by administration of clozapine, D-cycloserine, flumazenil, or SHC50911, a gamma-aminobutyrate B (GABA(B)) receptor antagonist. A decrease in the number of parvalbumin-positive cells and spine density in the frontal cortex, nucleus accumbens and hippocampus were evident in the brains of PCP-treated mice. Measurement of brain monoamine and their metabolite contents in adulthood indicated brain area-dependent and neurotransmitter-specific changes in monoamine metabolism. These findings suggest that neonatal treatment with PCP in mice leads to enhanced sensitivity to PCP and impairment of spatial working memory and social interaction behaviors in adulthood, which may be associated with reduced spine density and GABAergic interneurons and changes in monoamine metabolism. Furthermore, pharmacologic experiments suggest the potential applicability of neonatally PCP-treated mice as a useful animal model for new antipsychotic drug screening.
Nakatani-Pawlak
Akiko
A
Kanazawa University Graduate School of Natural Science and Technology, Kakuma-machi, Japan.
Yamaguchi
Kazumasa
K
Tatsumi
Yoshimi
Y
Mizoguchi
Hiroyuki
H
Yoneda
Yukio
Y
D000375:Aging / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D015306:Biogenic Monoamines / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000473:pathology*; D001923:Brain Chemistry / Q000187:drug effects* / Q000502:physiology; D007398:Interpersonal Relations; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010622:Phencyclidine / Q000633:toxicity*; D012559:Schizophrenia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology
D015306:Biogenic Monoamines; D010622:Phencyclidine