Cocaine use not only depends on the reinforcing properties of the drug, but also on its pharmacological effects on alternative nondrug activities. In animal models investigating choice between cocaine and alternative sweet rewards, the latter influence can have a dramatic impact on choice outcomes. When choosing under cocaine influence is prevented by imposing sufficiently long intervals between choice trials, animals typically prefer the sweet reward. However, when choosing under the drug influence is permitted, animals shift their preference in favor of cocaine.
We previously hypothesized that this preference shift is mainly due to a direct suppression of responding for sweet reward by cocaine pharmacological effects. Here we tested this hypothesis by making rats tolerant to this drug-induced behavioral suppression.
Contrary to our expectation, tolerance did not prevent rats from shifting their preference to cocaine when choosing under the influence.
Thus, other mechanisms must be invoked to explain the influence of cocaine intoxication on choice outcomes.