A Cocaine Context Renews Drug Seeking Preferentially in a Subset of Individuals

Abstract

Addiction is characterized by a high propensity for relapse, in part because cues associated with drugs can acquire Pavlovian incentive motivational properties, and acting as incentive stimuli, such cues can instigate and invigorate drug-seeking behavior. There is, however, considerable individual variation in the propensity to attribute incentive salience to reward cues. Discrete and localizable reward cues act as much more effective incentive stimuli in some rats ('sign-trackers', STs), than others ('goal-trackers', GTs). We asked whether similar individual variation exists for contextual cues associated with cocaine. Cocaine context conditioned motivation was quantified in two ways: (1) the ability of a cocaine context to evoke conditioned hyperactivity and (2) the ability of a context in which cocaine was previously self-administered to renew cocaine-seeking behavior. Finally, we assessed the effects of intra-accumbens core flupenthixol, a nonselective dopamine receptor antagonist, on context renewal. In contrast to studies using discrete cues, a cocaine context spurred greater conditioned hyperactivity, and more robustly renewed extinguished cocaine seeking in GTs than STs. In addition, cocaine context renewal was blocked by antagonism of dopamine receptors in the accumbens core. Thus, contextual cues associated with cocaine preferentially acquire motivational control over behavior in different individuals than do discrete cues, and in these individuals the ability of a cocaine context to create conditioned motivation for cocaine requires dopamine in the core of the nucleus accumbens. We speculate that different individuals may be preferentially sensitive to different 'triggers' of relapse.

Transient inactivation of the paraventricular nucleus of the thalamus enhances cue-induced reinstatement in goal-trackers, but not sign-trackers

“…6d). These data further highlight the notion that GTs and STs capture different forms of reward learning, both of which may be relevant to addiction liability (Saunders and Robinson 2010, Saunders et al 2013, Saunders et al 2014, Kawa et al 2016, Pitchers et al 2017), and both of which appear to be mediated by the PVT (Haight and Flagel 2014, Haight et al 2015, Haight et al 2017). …”

Adolescent cocaine exposure enhances goal-tracking behavior and impairs hippocampal cell genesis selectively in adult bred low-responder rats

“…For example, ablating neurogenesis in the hippocampus during forced abstinence following cocaine self-administration increases the propensity for context-dependent reinstatement (Noonan et al 2010), while reducing the number of adult-born hippocampal neurons increases time spent in a cocaine-paired context in a test of conditioned place preference (Castilla-Ortega et al 2016b). These data are congruent with the fact that goal-trackers appear to be more susceptible to reinstatement in response to drug-associated contexts (Saunders et al 2014) and that bLR rats are more sensitive to changes in hippocampal neurogenesis. Taken together, the relationship between adolescent cocaine exposure, the regulation of hippocampal cell genesis, and the enhanced expression of goal-tracking behavior suggested by the current findings, warrants further investigation.…”

“…Thus, while sign-trackers are more responsive to discrete drug-associated cues (Flagel et al 2011; Yager et al 2014) and more likely to exhibit cue- and drug-induced reinstatement of drug-seeking behavior relative to goal-trackers (Saunders and Robinson 2010, 2011) after relatively brief periods of cocaine self-administration, both phenotypes exhibit addiction-related behaviors following prolonged intermittent access to cocaine (Kawa et al 2016). In addition, goal-trackers have been shown to exhibit enhanced reinstatement of drug-seeking behavior in response to drug-associated contexts (Saunders et al 2014). Similar to outbred goal- and sign-trackers, we have postulated that bLRs and bHRs may represent two distinct paths to “addiction”.…”

MAM (E17) rodent developmental model of neuropsychiatric disease: disruptions in learning and dysregulation of nucleus accumbens dopamine release, but spared executive function

“…Schizophrenics also have a disproportionately high incidence of substance abuse (Dixon 1999;Dixon et al 1991;Gearon et al 2001), which could also be linked to alterations in the neural circuits that control the assignment of motivational value to reward (drug)-paired stimuli. We trained MAM and sham animals in a Pavlovian conditioned approach task that affords the opportunity to characterize the acquisition of a cue-reward association, as well as the attribution of incentive salience, the latter being predictive of multiple behaviors reminiscent of drug addiction (Saunders et al 2014;Saunders and Robinson 2010;Saunders et al 2013). In the present study, we found no strong evidence for a difference between MAM and sham animals in terms of the target or magnitude of their cue-triggered approach behavior, when such behavior was triggered.…”