PharmacologyBiochemistry& Behavior, Vol. 35, pp. 477--479.© Pergamon Pressplc, 1990.Printed in the U.S.A. 0091-3057/90$3.00 + .00 BRIEF COMMUNICATION Tolerance and Sensitization to Chronic and Subchronic Oral Caffeine: Effects on Wheelrunning in Rats I C. J. MELISKA, R. E. LANDRUM 2 AND T. A. LANDRUM Department of Psychology, Southern Illinois University at Carbondale Carbondale, IL 62901-6502 Received 13 February 1989 MELISKA, C. J., R. E. LANDRUMAND T. A. LANDRUM. Tolerance and sensitization to chronic and subchronic oral caffeine: Effects on wheelrunning in rats. PHARMACOL BIOCHEMBEHAV35(2) 477-479, 1990.--Twenty-four male Sprague-Dawley rats were tested for wheelrunning in conjunction with chronic (continuous) or subchronic(alternateday) oral caffeine administration. As expected, chronic administration led to complete tolerance to caffeine's locomotorstimulanteffect, while subchronic administration produced sensitization. Results confirm earlier reports of enhancedstimulation with spaced administration of caffeine and tolerance with chronic administration. Caffeine Wheelrunning Chronic administration Subchronic administration CAFFEINE has been characterized as the most widely used psychoactive drug in the world (5). While tolerance development in humans has been recognized for two decades (6), laboratory studies of tolerance to caffeine in animals have appeared only recently (I, 2, 7). The present study was designed to replicate earlier findings regarding tolerance to oral administration of caffeine using a different activity measure, wheelnmning. Further- more, we wished to examine the effect of spacing of caffeine administration, since we previously observed that stimulation of wheelrunniug is increased by repeated IP injections of caffeine when doses are separated by 48 or 72 hours (9,10). The present study compares the effects of repeated oral caffeine ingestion under conditions of chronic (consecutive days) vs. subchronic (alternate days) administration. We expected to observe tolerance to locomotor stimulation with chronic administration, but an increase in stimulation with subehronic administration. METHOD Subjects Subjects were 24 male Sprague-Dawley rats (SASCO, Omaha NE), approximately 210 days old, whose weights at the start of the study ranged between 442 and 553 g (mean=504, s.d. = 33). Light was provided from 0800 to 1630 daily. Apparatus Rats were housed individually in 8 standard activity wheels (Wahmann Mfg., Baltimore), 36 cm in diameter x 11 cm wide, with resting cages attached to each. Wheels were isolated in separate rooms. The sliding door separating the resting cage from each wheel was wired open. Animals occupied these cages with free access to the wheels for the duration of the study. Standard lab chow was available ad lib. Procedure Three groups of 8 rats each were randomly assigned to one of three drug conditions: chronic caffeine access (0.5 mg/ml hydrous caffeine alkaloid/Merck), subchronic caffeine access (24 hr of 0.5 mg/ml caffeine solution alternating with 24 hr tap water), or continuous tap water access. On the first two days of testing, all animals received tap water to establish baseline wheelrunning levels. Animals remained in the cages and wheels for 18 days--2 baseline days and 16 testing days, For the subehronic caffeine group, drinking solutions (either caffeine or tap water) were switched at 0930 daily. Drinking bottles were weighed daily, 1Portions of this study were presented at the November 1988 Society for NeuroscienceMeeting in Toronto, Ontario, Canada. 2present address" Departmentof Psychology, Universityof Wisconsin-Platteville, Platteville,WI 53818. 477