Choosing between cocaine and sucrose under the influence: testing the effect of cocaine tolerance

Abstract

Cocaine use not only depends on the reinforcing properties of the drug, but also on its intoxicating 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 cocaine intoxication at the moment of choice 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 intoxication. 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.

Oxytocin and orexin systems bidirectionally regulate the ability of opioid cues to bias reward seeking

“…This may account, in part, for the more equal preference between food and heroin observed under the choice conditions used here. Alternatively, more recent work suggests that the interval between choice trials, and the pharmacodynamics of the drug (in this case, heroin), are critical factors that impact choice behavior [70,71]. When comparing between two different rewards like food and heroin, EV is a useful metric, as it provides a normalization of the primary variable α, indicative of demand Fig.…”