Acute and chronic effects of delta 9-tetrahydrocannabinol on complex behavior of squirrel monkeys.

Squirrel monkeys were trained to press either two (phase one) or five (phase two) differently colored keys sequentially. Food presentation resulted if colors were pressed in a specific order, and high levels or accuracy were generated. Acutely, delta 9-tetrahydrocannabinol reduced accuracy and rate of responding in a dose-related fashion under both the two-key and five-key conditions. Responding, however, was more sensitive to the drug under the five-key procedure. Accuracy of responding at the beginning of a sequence tended to be more sensitive to drug effects than responding near the end. Daily (chronic) administration resulted in the development of tolerance to both the rate- and accuracy-reducing effects of the drug, although tolerance developed more rapidly to the accuracy-reducing effects. Tolerance developed more slowly under the five-key procedure than under the two-key procedure. Details of tolerance development were related to aspects of acute effects, suggesting that some facets of tolerance development may be predictable from acute drug effects.