TY - JOUR
T1 - Prenatal phencyclidine treatment induces behavioral deficits through impairment of GABAergic interneurons in the prefrontal cortex
AU - Toriumi, Kazuya
AU - Oki, Mika
AU - Muto, Eriko
AU - Tanaka, Junko
AU - Mouri, Akihiro
AU - Mamiya, Takayoshi
AU - Kim, Hyoung Chun
AU - Nabeshima, Toshitaka
N1 - Publisher Copyright:
© 2016, Springer-Verlag Berlin Heidelberg.
PY - 2016/6/1
Y1 - 2016/6/1
N2 - Rationale: We previously reported that prenatal treatment with phencyclidine (PCP) induces glutamatergic dysfunction in the prefrontal cortex (PFC), leading to schizophrenia-like behavioral deficits in adult mice. However, little is known about the prenatal effect of PCP treatment on other types of neurons. Objectives: We focused on γ-aminobutyric acid (GABA)-ergic interneurons and evaluated the effect of prenatal PCP exposure on the neurodevelopment of GABAergic interneurons in the PFC. Methods: PCP was administered at the dose of 10 mg/kg/day to pregnant dams from embryonic day 6.5 to 18.5. After the pups were reared to adult, we analyzed their GABAergic system in the PFC using immunohistological, biochemical, and behavioral analyses in adulthood. Results: The prenatal PCP treatment decreased the density of parvalbumin-positive cells and reduced the expression level of glutamic acid decarboxylase 67 (GAD67) and GABA content of the PFC in adults. Additionally, prenatal PCP treatment induced behavioral deficits in adult mice, such as hypersensitivity to PCP and prepulse inhibition (PPI) deficits. These behavioral deficits were ameliorated by pretreatment with the GABABreceptor agonist baclofen. Furthermore, the density of c-Fos-positive cells was decreased after the PPI test in the PFC of mice treated with PCP prenatally, and this effect was ameliorated by pretreatment with baclofen. Conclusions: These findings suggest that prenatal treatment with PCP induced GABAergic dysfunction in the PFC, which caused behavioral deficits.
AB - Rationale: We previously reported that prenatal treatment with phencyclidine (PCP) induces glutamatergic dysfunction in the prefrontal cortex (PFC), leading to schizophrenia-like behavioral deficits in adult mice. However, little is known about the prenatal effect of PCP treatment on other types of neurons. Objectives: We focused on γ-aminobutyric acid (GABA)-ergic interneurons and evaluated the effect of prenatal PCP exposure on the neurodevelopment of GABAergic interneurons in the PFC. Methods: PCP was administered at the dose of 10 mg/kg/day to pregnant dams from embryonic day 6.5 to 18.5. After the pups were reared to adult, we analyzed their GABAergic system in the PFC using immunohistological, biochemical, and behavioral analyses in adulthood. Results: The prenatal PCP treatment decreased the density of parvalbumin-positive cells and reduced the expression level of glutamic acid decarboxylase 67 (GAD67) and GABA content of the PFC in adults. Additionally, prenatal PCP treatment induced behavioral deficits in adult mice, such as hypersensitivity to PCP and prepulse inhibition (PPI) deficits. These behavioral deficits were ameliorated by pretreatment with the GABABreceptor agonist baclofen. Furthermore, the density of c-Fos-positive cells was decreased after the PPI test in the PFC of mice treated with PCP prenatally, and this effect was ameliorated by pretreatment with baclofen. Conclusions: These findings suggest that prenatal treatment with PCP induced GABAergic dysfunction in the PFC, which caused behavioral deficits.
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U2 - 10.1007/s00213-016-4288-8
DO - 10.1007/s00213-016-4288-8
M3 - Article
C2 - 27095448
AN - SCOPUS:84964329846
SN - 0033-3158
VL - 233
SP - 2373
EP - 2381
JO - Psychopharmacology
JF - Psychopharmacology
IS - 12
ER -