In Reply:—Thank you for giving us the opportunity to respond to Weinberger and Gold's letter. We apologize for not citing the article by Gold et al. [1] and for underestimating the durability of conditioned fear. When we stated [2] that “… we could not replicate the essential aspects [italics added] of one study [referring to Weinberger et al. [3]],” it was apparent that, although both groups used classic conditioning paradigms, our results were different, and we could not replicate learning and memory during anesthesia. Weinberger and Gold suggest that we should have used the term “extension” rather than “replication.” We have no objection, if this leads to better clarity for the reader. Weinberger and Gold expand on the differences between the two studies, which we have cited in our paper, but these differences cannot account for, in our opinion, the startling differences in the results, i.e., epinephrine enabling learning in anesthetized subjects but failing to do so in subjects receiving subanesthetic doses. Rabbits are more resistant than rats to the effects of anesthetics; enhancement of learning and memory by epinephrine should be more apparent with subanesthetic rather than anesthetizing doses, and a shorter retention interval should favor a more durable memory. [1] Even if fear conditioning is acquired more rapidly than the nictitating membrane conditioned response, our use of six training sessions and 360 training trials versus 1 and 10, respectively, by Weinberger et al. should mitigate any contribution of the different behavioral assays of conditioning in the two studies to the differing results. Weinberger and Gold suggest that the doses of epinephrine used may explain our different findings. This is unlikely. A look at Figure 5 [2] shows that we obtained the same pattern of enabling effects of epinephrine doses as Weinberger et al., 0.01 mg/kg epinephrine producing a better effect on learning than 0.1 mg/kg. Therefore, the use of larger doses could not have improved our results. We also had limited preliminary results using Sus-Phrine epinephrine, which suggested that smaller doses of epinephrine might not be effective in enabling learning in isoflurane-treated animals.
Finally, investigators in the area of learning and memory during anesthesia stress the importance of replication of earlier studies in this field. [4,5] To quote from a recent correspondence on the subject. [5]“Without replication and given the number of negative findings, all evidence for memory during anaesthesia may always be interpreted as chance findings.” It is, therefore, our sincere hope that Weinberger and Gold and other talented researchers will extend the results of the two studies referred to in these letters using a stable anesthetic concentration of a drug currently used in clinical practice.
M. M. Ghoneim, M.D.; Professor; Department of Anesthesia; The University of Iowa; Iowa City, Iowa 52242.
(Accepted for publication October 3, 1994.)
