Propofol Enhances Memory Formation via an Interaction with the Endocannabinoid System

Background: Propofol is associated with postoperative mood alterations and induces a higher incidence of dreaming compared with other general anesthetics. These effects might be mediated by propofol's inhibitory action on fatty acid amide hydrolase, the enzyme that degrades the endocannabinoid anandamide. Because propofol is also associated with a higher incidence of traumatic memories from perioperative awareness and intensive care unit treatment and the endocannabinoid system is involved in regulating memory consolidation of emotional experiences, the authors investigated whether propofol, at anesthetic doses, modulates memory consolidation via an activation of the endocannabinoid system. Methods: Male Sprague-Dawley rats were trained on an inhibitory avoidance task in which they received an inescapable foot shock upon entering the dark compartment of the apparatus. Drugs were administered intraperitoneally immediately or 30, 90, or 180 min after training. On the retention test 48 h later, the latency to reenter the dark compartment was recorded and taken as a measure of memory retention. Results: The anesthetic doses of propofol administered after training significantly increased latencies of 48-h inhibitory avoidance performance (483.4 +/- 181.3, 432.89 +/- 214.06, 300 and 350 mg/kg, respectively; mean +/- SD) compared with the corresponding vehicle group (325.33 +/- 221.22, mean +/- SD), which is indicative of stronger memory consolidation in propofol treated rats. Administration of a non-impairing dose of the cannabinoid receptor antagonist ri-monabant blocked the memory enhancement induced by propofol (123.39 +/- 133.10, mean +/- SD). Delayed administration of propofol 90 and 180 min after training or immediate posttraining administration of the benzodiazepine midazolam or the barbiturate pentobarbital did not significantly alter retention. Conclusions: These findings indicate that propofol, in contrast to other commonly used sedatives, enhances emotional memory consolidation when administered immediately after a stressful event by enhancing endocannabinoid signaling.