| Abstract: |
Introduction: Drugs can impair memory by a specific amnesic or a sedative effect. We used propofol (PRP) and thiopental (THP) to differentiate these mechanisms behaviorally. A continuous recognition test (CRT) was used to index working (6 secs) and encoding/acquisition (33 secs) memory function. Word recognition at the end of the day was used to test consolidation and long term memory. Methods: After informed consent, 83 R handed subjects (Ss), (32 F; median 30 yrs, 72 kg) were given PRP (n=30), THP (n=31) dexmedetomidine (n=10) or placebo (n=12) at one of 3 sedative/sleep doses using Stanpump (S. Shafer; http://anesthesia.stanford.edu/pkpd). Only responsive subjects receiving PRP/THP (n=46) are reported here. The CRT was done 52+-9.5 min before, and then during drug effect. The CRT presents 220 words (ISI 3 sec) with about half repeated once after a lag of 1 or 10 words. Reaction time (RT) was obtained when Ss pressed one of two buttons to indicate a new or old (repeated) word. Recognition scores were obtained several hours later to a list of previously presented words and distractors. All stimuli were presented auditorily, and all scores represent correct responses to lag 10 words. Ss were classified as High or Lowperformers using a median split of correct old's during the drug CRT (median for PRP: 48%, THP: 42%). Data from n=9 Ss were excluded (Plac n=3, PRP n=4, THP n=2 for any of : <50% score at baseline, missing data at Recognition, interruptions in the infusion, or absence of detectable drug effect). ANOVA was used with a priori contrasts to the Placebo group, with a post-hoc contrast of PRP-High to THP-High. Results: All groups performed similarly at Baseline. Ss receiving low dose PRP (Highperformers) performed similarly to Plac on the memory task. Recognition of old words during drug (heard 2X) was 61% for Plac and 36% for all drugs combined. The administration of drug did not affect recognition of baseline words (small box in Fig). PRP had a differential effect on information loss ("decrement") for words encoded during drug (see Fig). It was significantly greater for PRP-High(-41+-23%; n=7) than for both Placebo (-12+-8%, n=8, P=.002) and THP High(-17+-19%, n=8, P<.02). Low performers (n=8 THP, n=9 PRP) had a significantly greater sedative effect (RT increase of 158 msec or 9%, p<0.05). There were no differences between groups in the rate of guessing (false alarms; 18.5+-12.6 %) during recognition. Conclusions: Propofol impairs memory both by a specific amnesic, as well as a sedative effect. The specific amnesic effect of propofol occurs at low sedative effect, is apparent only on initially encoded stimuli, and is effected some time after exposure to stimuli (30 sec to 50 min). This amnesic mechanism is distinguishable from sedation, which interferes with initial encoding/acquisition of material. The specific amnesic effect of propofol occurs by interference with consolidation of successfully acquired material over a critical time period of about 50 minutes. |
