Perioperative Medicine

Background: It has been reported that bilateral lesions of the basolateral amygdala complex (BLA) blocked propofolinduced 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 -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 l) or saline (0.5 l) 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. DESPITE being a well-established clinical phenomenon, the molecular and cellular mechanism of anesthetic-induced amnesia remains poorly understood. Both postoperative cognitive dysfunction and intraoperative awareness have been distressing problems and continue to attract public attention; however, it is still not clear whether anesthetic drugs have anything to do with these two issues per se. Therefore, to communicate something about the potential of anesthetic drugs to contribute to such issues in ways we do not yet know, more work is needed to elucidate how these powerful drugs work in the brain. Extensive evidence from animal and human studies indicates that emotionally charged events are typically better remembered than neutral ones. The amygdala, particularly the basolateral amygdala (BLA), is a key structure in emotional processing in the brain. It has also been reported that bilateral BLA lesions block the memory-modulating effect of diazepam, propofol, and sevoflurane. In the current study, we investigated the mechanism underlying propofol produced amnesia and the necessity for the integrity of the BLA. The study was designed on the basis of the following findings. First, the -aminobutyric acid–mediated (GABAergic) system within the BLA is involved in memory modulation, whereas propofol has a predominant effect on enhancing -aminobutyric acid type A (GABAA) receptor function. 18–20 Second, the BLA modulates memory consolidation via its projections into the perirhinal cortex, postrhinal cortex, and hippocampus. The BLA–hippocampus interactions have attracted the most attention. Third, activityregulated cytoskeletal protein (Arc) plays an important role in the synaptic plasticity underlying the consolidation of long-term memory. Changes in Arc expression are recognized as an indicator of such synaptic plasticity. Alkire et al. found in their study that amnesic doses of the inhalational anesthetics sevoflurane and desflurane could reduce hippocampal Arc protein expression in rats with inhibitory avoidance (IA) training. Here, we proposed the hypothesis that propofol induces amnesia by increasing GABAergic activity in the BLA. To test this hypothesis, rats trained with IA were systemically given propofol with or without GABAA receptor inhibition by either BLA-injected bicuculline (a This article is accompanied by an Editorial View. Please see: Alkire MT, Guzowski JF: Hypothesis: Suppression of memory protein formation underlies anesthetic-induced amnesia. ANESTHESIOLOGY 2008; 109:768–70.