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GRANT APPLICATION No. 623C Subject: Walter B. Essman, M.D., Ph.D., Queens College of the City University of New York, Flushing Continuation application "Studies of Nicotine Action upon Memory Consolidation" Stripped to its essentials, this proposal is for continuing study for a projected three years, of the modulating effects of nicotine in mice on loss of a conditioned behavior reaction, and the influence of each of three stimuli said to produce "amnesic responses". These stimuli are electroshock, intrahippocampal 5-HT, and intraperitoneal injection of short-chain fatty acids. These will be correlated with changes in the 5-8T content of brain tissue, and effects on protein synthesis in that organ as measured by C14-leucine incorporation. Additional variables involve: 1. The use of three strains of mice varying in capacity to be conditioned. 2. Dosage of nicotine or its metabolites. 3. Time relationships of the administration of nicotine and the "amnesic stimulus". Some results are alrezdy anticipated by the applicant, and outlined in some detail. One of the difficulties in this study as projected is that the effects of at least one "amnesic stimulus", e.g. electroshock, as described in a lengthy progress report to CTR, No. 836 (10/1/72-7/15/73) involves many other facets of metabolism, of which adrenal cortical function is only one example. Thus, while effects on 5-HT and "protein synthesis" seem to correlate with alterations in conditioned rpsponse, this may be fortuitous, and not a cause and effect relationship. I therefore have concerns about the soundness of this work, with its numerous complex- ities both in its behavioral and biochemical parameters. Remarkably, the complex studies are being performed apparently by nnly two persons officially involved. Some portions of this application and of the progress report are difficult to understand (see letter, Liebc*.+ to Nordsiek, 10/14/74). Possibly this is a work of genius, but before drawing any such conclusions it should be subjected to a searching review by experts in psychopharmacology. I , would suggest Dr. Arnold Mandell, CLai rman of the Department of Psychiatry at the University of California, San Divi as one highly suitable person for this task. AAL/jp 10/14/74 Averill A. Liebow, M.D. b~ <Gy rr(& r i F I