Pharmacology Biochemistry and Behavior, Vol.45, pp. 225-228, 1993 0091-3057/93$6.00 + .00 Printedin the U.S.A.All rightsreserved. Copyright© 1993 Pergamon PressLtd. RAPID COMMUNICATION Effect of Anisomycin on the Development of Rapid Tolerance to Ethanol-Induced Motor Impairment MARCELA BITRAN 1 AND HAROLD KALANT 2 Department of Pharmacology, Medical Sciences Building, University of Toronto, Toronto M5S 1AS, Canada, and Addiction Research Foundation of Ontario, Toronto MSS 2S1, Canada Received 6 October 1992 BITRAN, M. AND H. KALANT. Effect of anisomycin on the development of rapid tolerance to ethanol-inducedmotor impairment. PHARMACOL BIOCHEM BEHAV 45(1) 225-228, 1993.-Male Wistar rats given a single moderate dose (1.7 g/kg, IP) of ethanol (EtOH), followed by six trials on the moving belt apparatus during the next hour, showed functional tolerance to the motor-impairing effects of a second dose given 24 h later if the first EtOH was preceded and followed by an injection of saline. The same EtOH dose and intoxicated practice did not produce tolerance if the saline injections were replaced by two doses of anisomycin (60 mg/kg each, SC) 15 rain before and 105 min after the first dose of EtOH. This finding suggests that rapid tolerance, like chronic tolerance, requires de novo synthesis of protein during a short period immediately related to the test experience. Ethanol Motor impairment Rapid tolerance Rat Anisomycin TOLERANCE to ethanol (EtOH) and other centrally acting drugs has been shown to occur in three different time frames, referred to as acute (within a single session) (13), rapid (de- monstrable in a second drug exposure 8-24 h after first) (3), and chronic (developing during repeated drug exposures over days or weeks) (7). The relationship among these three forms of tolerance is still the subject of much investigation, but it is known that all three forms can be facilitated by the opportu- nity to practice the tested task while under the effect of the drug (1,6,9,12). It is also known that chronic tolerance, like learning, is impaired by the action of inhibitors of cerebral protein synthesis, such as cycloheximide, during the time of the drug exposure (15). It therefore seemed useful to test whether rapid tolerance is similarly dependent upon de novo protein synthesis. In the present study, another inhibitor of protein synthesis, anisomycin, has been tested for its effects on the development of rapid tolerance to EtOH-induced motor impairment in the rat. Anisomycin has the advantage that its duration of action as an inhibitor of protein synthesis is much shorter than that of cycloheximide; a dose that produces 80070inhibition of cere- bral protein synthesis lasts for only about 2 h in the mouse (5). Therefore, by using anisomycin it is possible to define more precisely the time period within which protein synthesis must occur to permit rapid tolerance to develop. METHOD Subjects Four groups of male Wistar rats (n = 15 per group), weighing about 150 g when purchased (Charles River, Mon- tr~ai, Canada), were individually housed in an environmen- tally controlled room at 21-23°C and 40070 relative humidity, with lighting on from 0700-1900 h. Water and standard Pur- ina Rat Chow were available ad lib. Moving Belt Test Training period. In the moving belt test (MBT), rats are trained to walk on a motor-driven metal mesh belt that moves 1 Current address: Departamento de Cienci~sFisiol6gicas, Facultad de Ciencias Biol6gicas, Universidad Cat61ica de Chile, Santiago, Chile. 2 To whom requests for reprints should be addressed. 225