NEFIRACETAM PREVENTS PROPOFOL-INDUCED ANTEROGRADE AND RETROGRADE-AMNESIA IN THE RODENT WITHOUT COMPROMISING QUALITY OF ANESTHESIA

Background: Propofol is a short-acting intravenous anesthetic agent. H owever, cognitive function remains depressed for several hours thereaf ter. We have evaluated the ability of nefiracetam, a novel cognition-e nhancing agent, to alleviate propofol-induced amnesia in a rodent mode l of learning Methods: Rats were trained in a one-trial step-through, light-dark passive avoidance paradigm. Propofol (10 and 75 mg/kg) was administered by the intraperitoneal route at 15 min before training an d separately at increasing times in the immediate 0-6 h post-training period (100 and 150 mg/kg). Nefiracetam, 9 mg/kg, was administered by the intraperitoneal route 1 h before training. Animals were tested for recall at the 12 h posttraining time, and after their killing, immuno cytochemistry was used to determine the increase in hippocampal neuron al polysialylation, an event associated with memory consolidation. Ind uction and duration of anesthesia induced by propofol was determined u sing tail pinch and pedal withdrawal reflexes. Results: Propofol-induc ed anterograde amnesia occurred in a dose-dependent manner. Induction of retrograde amnesia required a higher dose of propofol, which anesth etized the animals and was effective only in the immediate 3-h post-tr aining period In the absence of any evident effect on the onset or dur ation of anesthesia, nefiracetam prevented both forms of propofol-indu ced amnesia and preserved the learning-associated changes of neuronal polysialylation state. Conclusions: The ability of nefiracetam to prev ent propofol-induced anterograde and retrograde amnesia is proposed to be indirect and to result from modulation of gene transcription in a manner that initiates a cascade of events involving protein synthesis leading to synaptic growth associated with the formation of the long-t erm memory trace.