Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Repeated Neonatal Propofol Administration Induces Sex-Dependent Long-Term Impairments on Spatial and Recognition Memory in Rats

  • Gonzales, Edson Luck T. (Department of Neuroscience, School of Medicine, and Neuroscience Research Center, SMART-IABS and KU Open Innovation Center, Konkuk University) ;
  • Yang, Sung Min (Department of Neuroscience, School of Medicine, and Neuroscience Research Center, SMART-IABS and KU Open Innovation Center, Konkuk University) ;
  • Choi, Chang Soon (Department of Neuroscience, School of Medicine, and Neuroscience Research Center, SMART-IABS and KU Open Innovation Center, Konkuk University) ;
  • Mabunga, Darine Froy N. (Department of Neuroscience, School of Medicine, and Neuroscience Research Center, SMART-IABS and KU Open Innovation Center, Konkuk University) ;
  • Kim, Hee Jin (Department of Pharmacy, Sahmyook University) ;
  • Cheong, Jae Hoon (Department of Pharmacy, Sahmyook University) ;
  • Ryu, Jong Hoon (Department of Oriental Pharmaceutical Science, Kyung Hee University) ;
  • Koo, Bon-Nyeo (Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine) ;
  • Shin, Chan Young (Department of Neuroscience, School of Medicine, and Neuroscience Research Center, SMART-IABS and KU Open Innovation Center, Konkuk University)
  • Received : 2014.10.17
  • Accepted : 2015.02.07
  • Published : 2015.05.01
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Abstract

Propofol is an anesthetic agent that gained wide use because of its fast induction of anesthesia and rapid recovery post-anesthesia. However, previous studies have reported immediate neurodegeneration and long-term impairment in spatial learning and memory from repeated neonatal propofol administration in animals. Yet, none of those studies has explored the sex-specific long-term physical changes and behavioral alterations such as social (sociability and social preference), emotional (anxiety), and other cognitive functions (spatial working, recognition, and avoidance memory) after neonatal propofol treatment. Seven-day-old Wistar-Kyoto (WKY) rats underwent repeated daily intraperitoneal injections of propofol or normal saline for 7 days. Starting fourth week of age and onwards, rats were subjected to behavior tests including open-field, elevated-plus-maze, Y-maze, 3-chamber social interaction, novel-object-recognition, passive-avoidance, and rotarod. Rats were sacrificed at 9 weeks and hippocampal protein expressions were analyzed by Western blot. Results revealed long-term body weight gain alterations in the growing rats and sex-specific impairments in spatial (female) and recognition (male) learning and memory paradigms. A markedly decreased expression of hippocampal NMDA receptor GluN1 subunit in female- and increased expression of AMPA GluR1 subunit protein expression in male rats were also found. Other aspects of behaviors such as locomotor activity and coordination, anxiety, sociability, social preference and avoidance learning and memory were not generally affected. These results suggest that neonatal repeated propofol administration disrupts normal growth and some aspects of neurodevelopment in rats in a sex-specific manner.

Keywords

References

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