Quantifying Individual Variation in the Propensity to Attribute Incentive Salience to Reward Cues

If reward-associated cues acquire the properties of incentive stimuli they can come to powerfully control behavior, and potentially promote maladaptive behavior. Pavlovian incentive stimuli are defined as stimuli that have three fundamental properties: they are attractive, they are themselves desired, and they can spur instrumental actions. We have found, however, that there is considerable individual variation in the extent to which animals attribute Pavlovian incentive motivational properties (“incentive salience”) to reward cues. The purpose of this paper was to develop criteria for identifying and classifying individuals based on their propensity to attribute incentive salience to reward cues. To do this, we conducted a meta-analysis of a large sample of rats (N = 1,878) subjected to a classic Pavlovian conditioning procedure. We then used the propensity of animals to approach a cue predictive of reward (one index of the extent to which the cue was attributed with incentive salience), to characterize two behavioral phenotypes in this population: animals that approached the cue (“sign-trackers”) vs. others that approached the location of reward delivery (“goal-trackers”). This variation in Pavlovian approach behavior predicted other behavioral indices of the propensity to attribute incentive salience to reward cues. Thus, the procedures reported here should be useful for making comparisons across studies and for assessing individual variation in incentive salience attribution in small samples of the population, or even for classifying single animals

Extinction and Latent Inhibition Involve a Similar Form of Inhibitory Learning that is Stored in and Retrieved from the Infralimbic Cortex

Extinction and latent inhibition each refer to a reduction in conditioned responding: the former occurs when pairings of a conditioned stimulus (CS) and an unconditioned stimulus (US) are followed by repeated presentations of the CS alone; the latter occurs when CS alone presentations precede its pairings with the US. The present experiments used fear conditioning to test the hypothesis that both phenomena involve a similar form of inhibitory learning that recruits common neuronal substrates. We found that the initial inhibitory memory established by extinction is reactivated in the infralimbic (IL) cortex during additional extinction. Remarkably, this reactivation also occurs when the initial inhibitory memory had been established by latent inhibition. In both cases, the inhibitory memory was strengthened by pharmacological stimulation of the IL. Moreover, NMDA receptor blockade in the IL disrupted the weakening in conditioned responding produced by either latent inhibition or extinction. These findings, therefore, indicate that latent inhibition and extinction produce a similar inhibitory memory that is retrieved from the IL. They also demonstrate that the IL plays a wide role in fear regulation by promoting the retrieval of inhibitory memories generated by CS alone presentations either before or after this CS has been rendered dangerous

Disruption of alcohol-related memories by mTORC1 inhibition prevents relapse

Relapse to alcohol abuse is a critical clinical issue, frequently caused by cue-induced drug craving. Therefore, disruption of the memory for the cue-alcohol association is expected to prevent relapse. It is increasingly accepted that memories become labile and erasable soon after their reactivation through retrieval, during a memory reconsolidation process that depends on protein synthesis. Here, we show that reconsolidation of alcohol-related memories triggered by the sensory properties of alcohol itself (odor and taste) activates mammalian target of rapamycin complex 1 (mTORC1) in select amygdalar and cortical regions in rats, resulting in increased levels of several synaptic proteins. Furthermore, systemic or central amygdalar (CeA) inhibition of mTORC1 during reconsolidation disrupts alcohol-cue associated memories, leading to a long-lasting suppression of relapse. Our findings provide evidence that the mTORC1 pathway and its downstream substrates play a crucial role in alcohol-related memory reconsolidation, and highlight this pathway as a therapeutic target to prevent relapse

Cocaine Cue-Induced Dopamine Release in Amygdala and Hippocampus:A High-Resolution PET [F-18]Fallypride Study in Cocaine Dependent Participants

Drug-related cues are potent triggers for relapse in people with cocaine dependence. Dopamine (DA) release within a limbic network of striatum, amygdala and hippocampus has been implicated in animal studies, but in humans it has only been possible to measure effects in the striatum. The objective here was to measure drug cue-induced DA release in the amygdala and hippocampus using high-resolution PET with [(18)F]fallypride. Twelve cocaine-dependent volunteers (mean age: 39.6±8.0 years; years of cocaine use: 15.9±7.4) underwent two [(18)F]fallypride high-resolution research tomography–PET scans, one with exposure to neutral cues and one with cocaine cues. [(18)F]Fallypride non-displaceable-binding potential (BP(ND)) values were derived for five regions of interest (ROI; amygdala, hippocampus, ventral limbic striatum, associative striatum, and sensorimotor striatum). Subjective responses to the cues were measured with visual analog scales and grouped using principal component analysis. Drug cue exposure significantly decreased BP(ND) values in all five ROI in subjects who had a high-, but not low-, craving response (limbic striatum: p=0.019, associative striatum: p=0.008, sensorimotor striatum: p=0.004, amygdala: p=0.040, and right hippocampus: p=0.025). Individual differences in the cue-induced craving response predicted the magnitude of [(18)F]fallypride responses within the striatum (ventral limbic: r=0.581, p=0.048; associative: r=0.589, p=0.044; sensorimotor: r=0.675, p=0.016). To our knowledge this study provides the first evidence of drug cue-induced DA release in the amygdala and hippocampus in humans. The preferential induction of DA release among high-craving responders suggests that these aspects of the limbic reward network might contribute to drug-seeking behavior