Prenatal phencyclidine treatment induces behavioral deficits through impairment of GABAergic interneurons in the prefrontal cortex.
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.



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.



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.



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 GABAB receptor 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.



These findings suggest that prenatal treatment with PCP induced GABAergic dysfunction in the PFC, which caused behavioral deficits.
Department of Chemical Pharmacology, Meijo University, Nagoya, Japan.|Project for Schizophrenia Research, Department of Psychiatry and Behavioral Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
Kazuya
K
Toriumi
Department of Chemical Pharmacology, Meijo University, Nagoya, Japan.
Mika
M
Oki
Department of Chemical Pharmacology, Meijo University, Nagoya, Japan.
Eriko
E
Muto
Department of Chemical Pharmacology, Meijo University, Nagoya, Japan.
Junko
J
Tanaka
Department of Chemical Pharmacology, Meijo University, Nagoya, Japan.|Division of Clinical Sciences and Neuropsychopharmacology, Meijo University, Nagoya, Japan.|Japanese Drug Organization of Appropriate Use and Research, Nagoya, Japan.
Akihiro
A
Mouri
Department of Chemical Pharmacology, Meijo University, Nagoya, Japan.|Japanese Drug Organization of Appropriate Use and Research, Nagoya, Japan.
Takayoshi
T
Mamiya
Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Korea Institute of Drug Abuse, Chunchon, South Korea.
Hyoung-Chun
HC
Kim
Japanese Drug Organization of Appropriate Use and Research, Nagoya, Japan. tnabeshi@ccalumni.meijo-u.ac.jp.|Nabeshima Laboratory, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tenpaku-ku, Nagoya, 468-8503, Japan. tnabeshi@ccalumni.meijo-u.ac.jp.|Advanced Diagnostic System Research Laboratory, Fujita Health University Graduate School of Health Sciences, Toyoake, Japan. tnabeshi@ccalumni.meijo-u.ac.jp.
Toshitaka
T
Nabeshima
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D005968:Glutamate Decarboxylase / Q000378:metabolism; D007395:Interneurons / Q000187:drug effects*; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D010320:Parvalbumins / Q000378:metabolism; D010622:Phencyclidine / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000254:growth & development; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000523:psychology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D018691:Excitatory Amino Acid Antagonists; D010320:Parvalbumins; D016760:Proto-Oncogene Proteins c-fos; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D010622:Phencyclidine
GABAergic neuron; Parvalbumin; Phencyclidine; Prefrontal cortex