Development of tolerance to the disruptive effects of cocaine on repeated acquisition and performance of response sequences

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Pigeons obtained food by making four responses on three keys in a specified sequence. Errors produced 5-second timeout periods, during which the keylights were off and responses had no effect. To establish a base line of repeated acquisition, the sequence of correct responses was changed from session to session. Cocaine (3 mg/kg) disrupted the behaviour: total errors increased, the relative frequency of perseverative errors increased, the rate of within-session error reduction (learning) decreased and the total trial time (pausing) increased. During repeated drug administration (30-50 sessions), these effects disappeared, i.e., tolerance developed. Tolerance did not develop, however, to cocaine-induced increases or decreases in timeout responding; such effects were nondisruptive in the sense that they did not reduce the rate of food reinforcement. For comparison, cocaine (3-10 mg/kg) was also studied under a 'performance' condition, in which the sequence of correct responses was the same from session to session. Cocaine increased performance errors and produced pausing, but tolerance developed more quickly than under the learning condition. The more rapid development of tolerance was presumably due to the stronger stimulus control of behavior under the performance condition.

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Journal of Pharmacology and Experimental Therapeutics

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