Abstract
The influence of environmental variables on the development of tolerance to physostigmine's effects in rats was examined using multiple fixed-ratio, extinction schedules of food presentation. Initial administration of physostigmine (0.4 mg/kg) produced nearly maximal decreases in the number of food pellets delivered, running response rate, and overall response rate, under multiple FR 10, EXT and multiple FR 50, EXT schedules. With repeated administration, tolerance to physostigmine's effects was observed when 10 responses were required to produce reinforcement but was not observed when 50 responses were required to produce reinforcement. Tolerance under the multiple FR 10, EXT schedule of reinforcement was also observed when physostigmine was administered post-session. When tolerance was acquired, it was retained for up to 25 drug-free days. These results suggest that tolerance to physostigmine's effects on schedule-controlled behavior is strongly influenced by response requirement, independent of physostigmine-induced reinforcement loss. Additionally, tolerance is not dependent on experience with the schedule while under the effects of physostigmine, and is retained for a substantial period of time in the absence of continued physostigmine administration.
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In conducting the research described in this report, the investigators adhere to the “Guide for the Care and Use of Laboratory Animals”, as promulgated by the Committee on Care and Use of Laboratory Animals of the Institute of Laboratory Animal Resources, National Research Council. The views of the authors do not purport to reflect the position of the Department of the Army or the Department of Defense, (para 4-3, AR 360-5)
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Genovese, R.F., Elsmore, T.F. & Witkin, J.M. Environmental influences on the development of tolerance to the effects of physostigmine on schedule-controlled behavior. Psychopharmacology 96, 462–467 (1988). https://doi.org/10.1007/BF02180025
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DOI: https://doi.org/10.1007/BF02180025