Abstract
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 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.
Conclusions
These findings suggest that prenatal treatment with PCP induced GABAergic dysfunction in the PFC, which caused behavioral deficits.
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Acknowledgments
This study was supported by the following: Grants-in-Aid for Scientific Research (C) (2646024 and 15K08218); Grants-in-Aid for Young Scientists (B) (26870878); Joint Research Project under the Japan-Korea Basic Scientific Cooperation Program; Program for Advancing Strategic International Networks to Accelerate the Circulation of Talented Researchers (S2603) from the Japan Society for the Promotion of Science (JSPS); Research Grants from the Ministry of Health, Labor, and Welfare of Japan; and Research Grant from the Smoking Research Foundation.
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The experimental procedures were approved by the Animal Experiment Committee of Meijo University (YakuJitsu-Nos. 9, 12, and 25). Procedures involving animals and their care were conducted according to international guidelines (National Research Council Committee 2011).
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The authors declare that they have no conflict of interest.
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Toriumi, K., Oki, M., Muto, E. et al. Prenatal phencyclidine treatment induces behavioral deficits through impairment of GABAergic interneurons in the prefrontal cortex. Psychopharmacology 233, 2373–2381 (2016). https://doi.org/10.1007/s00213-016-4288-8
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DOI: https://doi.org/10.1007/s00213-016-4288-8