Instant Transformation of Learned Repulsion into Motivational “Wanting”

Abstract

Summary Background Learned cues for pleasant rewards often elicit desire, which in addicts may become compulsive. According to the dominant view in addiction neuroscience and reinforcement modeling, such desires are the simple products of learning, coming from past association with reward outcome. Results We demonstrate that cravings are more than merely the product of accumulated pleasure memories: even a repulsive learned cue for unpleasantness can become suddenly desired via activation of mesocorticolimbic circuitry. Rats learned repulsion toward a Pavlovian cue (briefly-inserted metal lever) that always predicted an unpleasant Dead Sea saltiness sensation. Yet upon first re-encounter in a novel sodium depletion state to promote mesocorticolimbic reactivity (reflected by elevated Fos activation in ventral tegmentum, nucleus accumbens, ventral pallidum, and orbitofrontal prefrontal cortex), the learned cue was instantly transformed into an attractive and powerful motivational magnet. Rats jumped and gnawed on the suddenly attractive Pavlovian lever cue, despite having never yet tasted intense saltiness itself as anything other than disgusting. Conclusions Instant desire transformation of a learned cue contradicts views that Pavlovian desires are based essentially on previously learned values (e.g., prediction error or temporal difference models). Instead desire is re-computed at re-encounter by integrating Pavlovian information with current brain/physiological state. This powerful brain transformation reversed strong learned revulsion into avid attraction. Applied to addiction, related mesocorticolimbic transformations (e.g., drugs, neural sensitization) of cues for already pleasant drug experiences could create even more intense cravings. This cue/state transformation helps define what it means to say that addiction hijacks brain limbic circuits of natural reward.

Where is the chocolate? Rapid spatial orienting toward stimuli associated with primary rewards

“…To the best of our knowledge, this is the first demonstration that the attentional modulation of rewardassociated stimuli critically depends on the flexible representation of the properties of the associated reward. The fact that attentional orienting is modulated by reward devaluation is congruent with experiments showing that reward devaluation procedures modulate behavior (e.g., Wellman et al, 2005) and brain activity (Gottfried et al, 2003) evoked by the reward-associated stimuli Recently, Robinson and Berridge (2013) have underlined the importance of the relevance of the reward's representation for the reactions elicited by reward-associated stimuli. They demonstrated that it is not only possible to diminish the behavioral reactions elicited by a CS through reward devaluation, but that it is also possible to amplify them by increasing the relevance of the associated reward for the current needs of the organism.…”

The role of learning-related dopamine signals in addiction vulnerability

“…It suggests, thus, that sign-trackers need a phasic dopaminergic prediction-error signal in order to learn because their learning is heavily biased towards learning through incremental acquisition of model-free values V MF (s). The fact that the signals are observed in the NAcc core also maps onto the notion that these signals might be model-free because, as discussed above, model-free mechanisms suffice for general PIT, which is dependent on the core, but not for specific PIT, which is more dependent on the shell (section 4.4; Corbit and Balleine 2011; though see (Shiflett and Balleine, 2010;Robinson and Berridge, 2013)). Finally, the reliance on model-free learning can, at least in part, explain the core incentive salience features.…”

“…Importantly, sign-tracking behavior was fully impaired upon the first CS-US presentation following administration of flupenthixol into the accumbens. Thus, the drug effects were evident before new learning could occur, and changes in in dopamine levels were able to alter the motivational value of reward cues, without the need to re-experience the CS-US association (Berridge, 2012;Richard et al, 2013;Dayan and Berridge, 2013;Robinson and Berridge, 2013). Furthermore, the effects of dopamine antagonism were specific to the Pavlovian conditioned approach behavior and did not affect the conditioned orienting response in the sign-trackers .…”

“…A striking example was recently provided by Robinson and Berridge (2013), where animals were first trained to associate a CS with aversive Dead Sea salty water, such that presentations of the CS readily induced aversive responses. Strikingly, after rendering the animals hungry for salt, they immediately started approaching the CS.…”

Input-specific contributions to valence processing in the amygdala

“…The ability of neurons to flexibly respond to reinforcers with either approach or avoidance behaviors also facilitates the explanation of counterintuitive behavioral choices. For example, extremely salty solutions are typically avoided, but physiological salt deprivation will produce approach behavior for salty reinforcers (Robinson and Berridge 2013). Also, cues that predict punishing reinforcers are also sometimes chosen over cues that predict the absence of any reinforcer (Barberini et al 2012).…”