SELF-ADMINISTRATION OF ACETYLSALICYLIC ACID AND COMBINATIONS WITH CODEINE AND CAFFEINE IN RHESUS MONKEYS

¹ Institut für Pharmakologie der Bayer AG, Wuppertal-Elberfeld, Germany

One group of rhesus monkeys was allowed to press a lever for intravenous injections of saline, another group for intravenous injections of codeine (0.05 mg/kg/injection). Saline was available 24 hours, codeine 3 hours per day. After lever pressing became stable, saline was replaced by acetylsalicylic acid (ASA, 2.5 and 10 mg/kg/injection), and codeine was replaced either by ASA or by combinations of ASA plus codeine, ASA plus caffeine, ASA plus caffeine plus codeine and by caffeine plus codeine. Intravenous acetylsalicylic acid at 2.5 mg/kg/injection generated rates of responding slightly above saline level in three out of four naive monkeys. With 10 mg/kg/injection of ASA, self-administration behavior was below the saline level. Further ASA (in doses from 0.4 to 25 mg/kg/injection did not maintain self-administration behavior previously generated by intravenous codeine (0.05 mg/kg/injection). Mixtures of ASA (2.5-25 mg/kg/injection) with codeine (0.05 and 0.2 mg/kg/injection), when offered to monkeys trained for codeine self-administration (0.05 mg/kg/injection), produced decreases in the number of codeine self-injections. Codeine intake was also decreased when these monkeys were pretreated with ASA (100 and 200 mg/kg i.v.) 15 to 180 minutes prior to the codeine self-administration sessions. Caffeine was not self-administered more frequently than saline, either when caffeine was offered alone (0.2 mg/kg/injection) or in a mixture with ASA (2.5 mg/kg/injection). A mixture of caffeine (0.2 mg/kg/injection) and codeine (0.05 mg/kg/injection) was taken at lower rates than solutions of codeine alone. When the three drugs were offered together in a mixture, the rates of self-administration were lower than those generated by ASA-codeine or caffeine-codeine mixtures as well as by codeine alone. The results of this study failed to show considerable positive reinforcing properties for ASA. Codeine intake was reduced when ASA was added to codeine in the self-administration solutions.

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