Bilateral inhibition of gamma-aminobutyric acid type A receptor function within the basolateral amygdala blocked propofol-induced amnesia and activity-regulated cytoskeletal protein expression inhibition in the hippocampus.

Background: It has been reported that bilateral lesions of the basolateral amygdala complex (BLA) blocked propofol-induced amnesia of inhibitory avoidance (IA) training. Based on these results, the authors hypothesized that the amnesia effect of propofol was partly due to its impairment of memory formation in the hippocampus through activating the BLA gamma-aminobutyric acid type A receptor function. The authors determined the changes in activity-regulated cytoskeleton-associated protein (Arc) expression to be an indicator of IA memory formation.

Methods: Male Sprague-Dawley rats received bilateral injection of bicuculline methiodide (10, 50, or 100 pmol/0.5 microl) or saline (0.5 microl) into the BLA. Fifteen minutes later, the rats were intraperitoneally injected with either propofol (25 mg/kg) or saline. After 5 min, the one-trial IA training was conducted. Rats intraperitoneally infused with saline served as controls and only received saline injections into the BLA. Twenty-four hours later, the IA retention latency was tested. Separate groups of rats treated the same way were killed either 30 min after IA training for hippocampal Arc mRNA measurement or after 45 min for protein level quantification.

Results: The largest dose of bicuculline methiodide (100 pmol) not only blocked the propofol-induced amnesia but also reversed the inhibition effect of propofol on Arc protein expression in the hippocampus (P < 0.05). However, the mRNA level of Arc showed no significant changes after propofol and bicuculline methiodide administration.

Conclusions: The amnesic effect of propofol seems to involve the modulation of Arc protein expression in the hippocampus, occurring through a network interaction with the BLA.