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

Abstract

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.

Figure 1

(A) Mean (+/− SEM) number of gapes/30 min for the High and the Low Gapers averaged across terminal Trials 15 and 16. (B) Mean (+/− SEM) number of gapes/30 min across Trials 1–16 for the High Gapers, the Low Gapers, and the Saline Controls. *, p <0.05; #, p <0.01; †, p <0.001.

Figure 2

(A) Mean (+/− SEM) Log10 latency (seconds) to make the first response on the active empty spout across Trials 1–16 for the High Gapers, the Low Gapers, and the Saline Controls. (B) Mean (+/− SEM) Goal-Directed behavior (i.e., active minus inactive spout responses/2 h.) for High Gapers, Low Gapers, and Saline Controls across Trials 1 – 16. (C) Mean (+/− SEM) Log10 latency (seconds) to earn the first infusions of saline or cocaine across Trials 1–16 for the Saline Controls and the Low and High Gapers. (D) Mean (+/− SEM) number of infusions/2 h for the High Gapers, the Low Gapers, and the Saline Controls across Trials 1–16. *, p <0.05; #, p <0.01; †, p <0.001.

Figure 3

(A) Mean (+/− SEM) Goal-Directed behavior (active minus inactive responses) during the 30 min intraoral infusion period for Low Gapers, High Gapers, and the Saline Controls across Trials 1–17. (B) Mean (+/− SEM) responses on the active spout during the 20 second time out (TO) period for the Low Gapers, the Higher Gapers, and the Saline Controls across Trials 1–16. *, p <0.05; #, p <0.01; †, p <0.001.