Biomol Ther.  2015 May;23(3):251-260. 10.4062/biomolther.2014.120.

Repeated Neonatal Propofol Administration Induces Sex-Dependent Long-Term Impairments on Spatial and Recognition Memory in Rats

• Gonzales E
• Yang SM
• Choi CS
• Mabunga DF
• Kim HJ
• Cheong JH
• Ryu JH
• Koo BN
• Shin CY

• KMID: 2380335
• DOI: http://doi.org/10.4062/biomolther.2014.120

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.

Keyword

Propofol; Anesthesia; Neurodevelopment; Sex-difference; Weight gain; Learning and memory

MeSH Terms

alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Anesthesia
Animals
Anxiety
Avoidance Learning
Blotting, Western
Body Weight
Humans
Injections, Intraperitoneal
Interpersonal Relations
Learning
Male
Memory*
Motor Activity
N-Methylaspartate
Propofol*
Rats*
Weight Gain
N-Methylaspartate
Propofol
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid