Amphetamine-induced sensitization and reward uncertainty similarly enhance incentive salience for conditioned cues.

Abstract

Amphetamine and stress can sensitize mesolimbic dopamine-related systems. In Pavlovian autoshaping, repeated exposure to uncertainty of reward prediction can enhance motivated sign-tracking or attraction to a discrete reward-predicting cue (lever CS+), as well as produce cross-sensitization to amphetamine. However, it remains unknown how amphetamine-sensitization or repeated restraint stress interact with uncertainty in controlling CS+ incentive salience attribution reflected in sign-tracking. Here rats were tested in three successive phases. First, different groups underwent either induction of amphetamine sensitization or repeated restraint stress, or else were not sensitized or stressed as control groups (either saline injections only, or no stress or injection at all). All next received Pavlovian autoshaping training under either certainty conditions (100% CS-UCS association) or uncertainty conditions (50% CS-UCS association and uncertain reward magnitude). During training, rats were assessed for sign-tracking to the lever CS+ versus goal-tracking to the sucrose dish. Finally, all groups were tested for psychomotor sensitization of locomotion revealed by an amphetamine challenge. Our results confirm that reward uncertainty enhanced sign-tracking attraction toward the predictive CS+ lever, at the expense of goal-tracking. We also report that amphetamine sensitization promoted sign-tracking even in rats trained under CS-UCS certainty conditions, raising them to sign-tracking levels equivalent to the uncertainty group. Combining amphetamine sensitization and uncertainty conditions together did not add together to elevate sign-tracking further above the relatively high levels induced by either manipulation alone. In contrast, repeated restraint stress enhanced subsequent amphetamine-elicited locomotion, but did not enhance CS+ attraction.

Roles of “Wanting” and “Liking” in Motivating Behavior: Gambling, Food, and Drug Addictions

“…For example, distal cues that are on the periphery of our attention are typically ignored under certain and predictable reward conditions, but when reward conditions are unpredictable, these cues attract more attention (Robinson et al 2014a). In fact the degree of incentive enhancement that uncertainty imparts to reward-related cues is similar to that produced by psychomotor sensitization through repeated amphetamine administration (Robinson et al 2015a). This may not come as a surprise considering that cues that predict an uncertain reward (50 % probability) produce a greater dopamine signal, originating from the ventral midbrain, during the anticipation of the uncertain outcome (Fiorillo et al 2003), and that this dopaminergic signal appears to promote risk-seeking behavior, as evidenced in gambling (Fiorillo 2011).…”

Elucidating the role of D4 receptors in mediating attributions of salience to incentive stimuli on Pavlovian conditioned approach and conditioned reinforcement paradigms

“…For instance, animals with a ST phenotype show greater locomotor sensitisation to cocaine administration and increased cocaine intake, leading to the suggestion that ST may represent a behavioural marker for addiction proneness [41,80]. Pharmacological agents broadly acting at D 2 -like receptors modulate ST [58,44,67]. Therefore, the lack of effect of the highly selective D 4 agonist PD168077 is significant, given the suggestion that D 4 receptors may play a crucial role in controlling attributions of salience to gambling-related stimuli (see [23] for discussion).…”

“…Lastly, the latency to nosepoke at the food hopper following presentation of the CS+ and CS-was also measured. Animals were labelled as either goal-or sign-trackers if they demonstrated at least a sixfold greater propensity to approach either the food hopper over the CS+ or vice versa, similar to [67]. Analysis were conducted with all animals, but based on an a priori assumption of differences within the groups, separate analyses were also conducted including only animals categorized as ST and GT.…”

“…The expression of both goal-and sign tracking appears contingent on DA, as perturbations to dopaminergic signaling via administration of D 2 -like agonists or antagonists impair the expression of both ST and GT [44,31]. In contrast, interventions that lead to augmented dopaminergic activity, such as amphetamine sensitisation, chronic stress or exposure to uncertainty lead to an increase in the acquisition of a ST over a GT response [67]. Conditioned stimuli signaling non-contingent food delivery has been linked with increased dopamine release in the core, but not the shell sub-region of the nucleus accumbens (NAc) [13].…”

For Value or for Worth? Part 2: A Neuroeconomical Thought-Action-Mood-Space Modulated by (Un-)Certainty as Sign- or Goal-tracking

“…Teasing through contextual unknowns increases ST further [50][51][52], maybe because then cues signal lesser efforts unreliably [53]. Tracking-attitude may also depend on status, which is partly inborn: Dominant members often eat first and submissive members are more successful if they use innovative hypotheses, i.e.…”