Does maternal administration of antipsychotics have a prophylactic effect on the development of psychotic features in offspring?: An animal study using the asphyxia model of schizophrenia.

• Project/Area Number: 22791118
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Psychiatric science
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: TAKAHASHI Taro 浜松医科大学, 子どものこころの発達研究センター, 特任研究員 (30402358)
• Co-Investigator(Renkei-kenkyūsha): SUZUKI Katsuaki 浜松医科大学, 子どものこころの発達研究センター, 特任准教授 (00285040) ; MATSUZAKI Hideo 浜松医科大学, 子どものこころの発達研究センター, 特任准教授 (00334970)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 精神薬理学 / 非定型抗精神病薬 / 統合失調症 / 神経幹細胞 / 仮死モデル / クロザピン / 早期介入

Research Abstract

The asphyxia model of schizophrenia, in which rat pups were exposed to 15 min of intrauterine anoxia during Cesarean section birth, showed a reduction in hippocampal dentate granule cells at 6 weeks of age and dopaminergic dysregulation at 12 weeks after birth, both have been regarded as schizophrenia-like phenotypes. Using this model, we examined in this study whether administration of antipsychotics to mothers prevent the development of schizophrenia-like features in their offspring. Pregnant female rats were administered daily either with clozapine(0. 5 or 5. 0 mg/kg), haloperidol(0. 1 or 1. 0 mg/kg), or saline by intraperitoneal infusions. Their pups were delivered Cesarean section with or without asphyxia. Twelve weeks after birth, pups were challenged with methamphetamine(0. 5 or 2. 0 mg/kg) or saline, and their locomotor activity were measured. As a result, there were no significant effects of either dose of clozapine or haloperidol on methamphetamine-induced locomotor activity in those pups.
These results failed to support the hypothesis that maternal administrations of antipsychotic might have a prophylactic effect on the development of psychotic features in their offspring.

Research Products

• [Journal Article] Plasma cytokine profiles in subjects with high-functioning autism spectrum disorders (2011)
  • Author(s): Suzuki K, Matsuzaki H, Iwata K, Kameno Y, Shimmura C, Kawai S, Yoshihara Y, Wakuda T, Takebayashi K, Takagai S, Matsumoto K, Tsuchiya KJ, Iwata Y, Nakamura K, Tsujii M, Sugiyama T, Mori N
  • Journal Title: PLoS One Volume: 6
• [Journal Article] Destruction of dopaminergic neurons in the midbrain by 6-hydroxydopamine decreases hippocampal cell proliferation in rats : reversal by fluoxetine (2010)
  • Author(s): Suzuki K, Okada K, Wakuda T, Shinmura C, Kameno Y, Iwata K, Takahashi T, Suda S, Matsuzaki H, Iwata Y, Hashimoto K, Mori N
  • Journal Title: PLoS One Volume: 5
  • NAID: 120005314217
• [Journal Article] Decreased serum levels of adiponectin in subjects with autism (2010)
  • Author(s): Fujita-Shimizu A, Suzuki K, Nakamura K, Miyachi T, Matsuzaki H, Kajizuka M, Shinmura C, Iwata Y, Suda S, Tsuchiya KJ, Matsumoto K, Sugihara G, Iwata K, Yamamoto S, Tsujii M, Sugiyama T, Takei N, Mori N
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry Volume: 34 Pages: 455-8
• [Journal Article] Failure to confirm genetic association of the FXYD6 gene with schizophrenia : the Japanese population and meta-analysis (2010)
  • Author(s): Iwata Y, Yamada K, Iwayama Y, Anitha A, Thanseem I, Toyota T, Hattori E, Ohnishi T, Maekawa M, Nakamura K, Suzuki K, Matsuzaki H, Tsuchiya KJ, Suda S, Sugihara G, Takebayashi K, Yamamoto S, Iwata K, Mori N, Yoshikawa T
  • Journal Title: Am J Med Genet B Neuropsychiatr Genet Volume: 153B Pages: 1221-7