A cocaine cue acts as an incentive stimulus in some but not others: implications for addiction

Abstract

Background: In addicts drug cues attract attention, elicit approach, and motivate drug-seeking and drug-taking behavior, and addicts find it difficult to resist such cues. In preclinical studies we have found, however, that food cues acquire incentive motivational properties only in a subset of individuals. For example, a food cue becomes attractive, eliciting approach and engagement with it, and acts as an effective conditional reinforcer in some rats but not others. We asked, therefore, whether rats that have a propensity to attribute incentive salience to a food cue are the same ones that attribute incentive value to a drug (cocaine) cue.

Methods: We first used a Pavlovian conditioned approach procedure to determine which individual rats attributed incentive salience to a food cue. A second cue was then associated with the IV self-administration of cocaine. Later, the ability of the cocaine cue to maintain self-administration behavior and to reinstate self-administration after extinction was assessed.

Results: We report that in individuals that had a propensity to attribute incentive salience to a food cue, a cocaine cue spurred motivation to take drugs (its removal greatly diminished self-administration) and reinstated robust drug-seeking after extinction. However, in those individuals that failed to attribute incentive salience to a food cue, the cocaine cue was relatively devoid of incentive motivational properties.

Conclusions: We conclude that it is possible to determine, before any drug experience, which individuals will most likely have difficulty resisting drug cues, a trait that might confer susceptibility to addiction.

Figure 1

Schematic illustrating the experimental design. All animals received identical Pavlovian conditioned approach (PCA) and cocaine self-administration acquisition training. Following acquisition, Experiment 1 (Exp. 1), and Experiment 2 (Exp. 2) diverged as shown. During self administration, the conditional stimulus (CS) was a nose poke port cue light and the unconditional stimulus (US) was an intravenous infusion of cocaine. Depending on the experimental phase, an active nose poke produced the CS and US (Acquisition/Re-Acquisition), the CS but no US (Cued Extinction), no CS but the US (Cue Removal), or nothing (X – Extinction).

Figure 2

Behavior directed towards the lever-CS (“sign-tracking”) or the food cup (the location of US delivery; “goal-tracking”) during the 8 s CS period on the final day of Pavlovian training. The topography of the conditional response (CR) is different in rats designated sign-trackers (STs, n=14) vs. goal-trackers (GTs, n=16). The mean ± SEM for (a) probability of approaching the lever [# trials with a lever contact/#trials per session] (CS) during the 8 s CS period, (b) number of lever contacts (c) latency to the first lever contact after CS presentation, (d) probability of approach to the food tray during the 8 s CS period, (e) number of food tray contacts during the CS period, and (f) latency to the first food tray entry after CS presentation. *, indicates significant group differences, p < 0.001.

Figure 3

Acquisition of cocaine self-administration behavior in sign-trackers (n=14) and goal-trackers (n=16). (a) The mean ± SEM number of cocaine infusions per minute for infusion criteria 5, 10, 15, and 25 (0.5 mg/kg/inf) and 40 and 80 (0.2 mg/kg/inf). (b) The mean ± SEM number of active and inactive nose poke responses at each infusion criterion.

Figure 4

Effects of removal of a cocaine-associated cue on self-administration behavior in sign-trackers (n=14) and goal-trackers (n=16). (a) The mean ± SEM number of cocaine infusions (0.2 mg/kg/infusion) per minute in sign-trackers and goal-trackers in the presence of the cocaine cue (sessions 1–3, 6–9) and when the light cue was not presented along with the injection of cocaine (sessions 4–5). (b) The rate of cocaine self-administration (infusions/min) for individual animals averaged over the baseline period (cocaine cue present, sessions 1–3) and the cue removal sessions (sessions 4–5). *, indicates a significant group difference, p < 0.05.

Figure 5

Extinction of responding for cocaine in sign-trackers (n=14) and goal-trackers (n=16), when a response continued to produce the cocaine-associated CS. (a) The mean ± SEM number of active responses for the CS, expressed in 4-session blocks. (b) The mean ± SEM number of active responses for the CS during the first 4 extinction sessions (effect of group, F_(1,85) = 4.57, p = 0.035). *, indicates a significant group difference, p < 0.05.

Figure 6

Cue-induced reinstatement of responding in sign-trackers (n=12) and goal-trackers (n=13). Following extinction, all animals were given a single, 60-min cue reinstatement test session, in which active responses resulted in presentation of the cocaine cue. (a) Mean ± SEM number of active port nose pokes in 10-min blocks over the 60-min session. (b) The total number of active port responses in individual animals (the solid horizontal line indicates the group mean and the dashed line the average number of responses at the inactive port). *, indicates a significant group difference, p < 0.05.