Conditioned Aversion for a Cocaine-Predictive Cue is Associated with Cocaine Seeking and Taking in Rats.

Rats emit aversive taste reactivity (TR) behavior (i.e., gapes) following intraoral delivery of a cocaine-paired taste cue, and greater conditioned aversive TR in well-trained rats predicts greater drug-taking. Here, we used a between-groups design and tracked the development of this conditioned aversive TR behavior on a trial by trial basis in an effort to determine when the change in behavior occurs and at what point individual differences in cue reactivity become predictive of cocaine-seeking and cocaine-taking. The results demonstrate that conditioned aversive TR to a cocaine-predictive flavor cue appears very early in training (i.e., following as few as 1 to 2 taste-drug pairings), stabilizes quickly, and becomes predictive of terminal self-administration within 3 to 4 trials. Indeed, rats exhibiting high conditioned aversive TR to the cocaine-paired cue also exhibited greater goal-directed behavior, were faster to take drug, self-administered more cocaine, and exhibited greater seeking during periods of drug non-availability. High conditioned aversive TR, then, develops quickly and is associated with a greater motivation for drug.