A selective role for dopamine in stimulus-reward learning

Abstract

Individuals make choices and prioritize goals using complex processes that assign value to rewards and associated stimuli. During Pavlovian learning, previously neutral stimuli that predict rewards can acquire motivational properties, becoming attractive and desirable incentive stimuli. However, whether a cue acts solely as a predictor of reward, or also serves as an incentive stimulus, differs between individuals. Thus, individuals vary in the degree to which cues bias choice and potentially promote maladaptive behaviour. Here we use rats that differ in the incentive motivational properties they attribute to food cues to probe the role of the neurotransmitter dopamine in stimulus-reward learning. We show that intact dopamine transmission is not required for all forms of learning in which reward cues become effective predictors. Rather, dopamine acts selectively in a form of stimulus-reward learning in which incentive salience is assigned to reward cues. In individuals with a propensity for this form of learning, reward cues come to powerfully motivate and control behaviour. This work provides insight into the neurobiology of a form of stimulus-reward learning that confers increased susceptibility to disorders of impulse control.

Figure 1. Development of sign-tracking vs. goal-tracking CRs in bHR and bLR animals, respectively

Behavior directed towards the lever-CS (sign-tracking) is shown in panels a-b and that directed towards the food-tray (goal-tracking behavior) in panels c-d (n=10/group). Mean + SEM (a) number of lever-CS contacts made during the 8-s CS period, (b) latency to the first lever-CS contact, (c) number of food-tray beam breaks during lever-CS presentation, (d) latency to the first beam break in the food-tray during lever-CS presentation. For all of these measures (a-d) there was a significant effect of phenotype, session, and a phenotype x session interaction (P≤0.0001). (e) Mean+ SEM probability of approach to the lever minus the probability of approach to the food-tray. A score of zero indicates that neither approach to the lever-CS nor approach to the food-tray was dominant. (f, g) Test for conditioned reinforcement illustrated as the mean + SEM number of active and inactive nose pokes in bred rats that received either paired (bHR, n=10; bLR, n=9) or pseudorandom (bHR, n=9; bLR, n=9) CS-US presentations. Rats in the paired groups poked more in the active port relative to random groups of the same phenotype (*P<0.02), but the magnitude of this effect was greater for bHRs (phenotype x group interaction, P=0.04).

Figure 2. Phasic dopamine signaling in response to CS and US presentation during the acquisition of Pavlovian conditioned approach behavior in bHR and bLR rats

Phasic dopamine release was recorded in the core of the nucleus accumbens using FSCV across six days of training. (a, d) Representative surface plots depict trial-by-trial fluctuations in dopamine concentration during the twenty-second period around CS and US presentation in individual animals throughout training. (b, e) Mean + SEM change in dopamine concentration in response to CS and US presentation for each session of conditioning. (c, f) Mean + SEM change in peak amplitude of the dopamine signal observed in response to CS and US presentation for each session of conditioning (n=5/group; Bonferroni post-hoc comparison between CS- and US-evoked dopamine release: *P<0.05; **P<0.01). Panels a-c demonstrate that bHR animals, which developed a sign-tracking CR, show increasing phasic dopamine responses to CS presentation and decreasing responses to US presentation across the six sessions of training. In contrast, panels d-f demonstrate that bLR rats, which developed a goal-tracking CR, maintain phasic responses to US presentation throughout training.

Figure 3. Conditonal responses and phasic dopamine signaling in response to CS and US presentation in outbred rats

Phasic dopamine release was recorded in the core of the nucleus accumbens using FSCV across six days of training. (a) Behavior directed towards the lever-CS (sign-tracking) and (b) that directed towards the food-tray (goal-tracking behavior) during conditioning. Learning was evident in both groups as there was a significant effect of session for rats that learned a sign-tracking response (n=6; session effect on lever contacts: F_(5,25) = 11.85, P = 0.0001) and for those that learned a goal-tracking response (n=5; session effect on food-receptacle contacts: F_(5,20) = 3.09, P = 0.03). (c, e) Mean + SEM change in dopamine concentration in response to CS and US presentation for each session of conditioning. (d, f) Mean + SEM change in peak amplitude of the dopamine signal observed in response to CS and US presentation for each session of conditioning. (Bonferroni post-hoc comparison between CS- and US- evoked dopamine release: *P<0.05; **P<0.01). Panels c-d demonstrate that animals developing a sign-tracking CR (n=6) show increasing phasic dopamine responses to CS presentation and decreasing responses to US presentation consistent with bHR animals. Panels e-f demonstrate that animals developing a goal-tracking CR (n=5) maintain phasic responses to US presentation consistent with bLR animals.

Figure 4. DA is necessary for learning CS-US associations that lead to sign-tracking, but not goal-tracking

The effects of flupenthixol are shown for: 1. Measures of sign-tracking: (a) probability to approach the lever-CS, (b) number of contacts with the lever-CS, (c) latency to contact the lever-CS. 2. Measures of goal-tracking: (d) probability to approach the food-tray during lever-CS presentation, (e) number of contacts with the food-tray during lever-CS presentation, (f) latency to contact the food-tray during lever-CS presentation. Data are expressed as mean + SEM. Flupenthixol (sessions 1–7) blocked the performance of both sign-tracking and goal-tracking CRs. To determine whether flupenthixol influenced performance or learning of a CR, behavior was examined following a saline injection on session 8 for all rats. bLR rats that were treated with flupenthixol prior to sessions 1–7 (bLR-Flu, n=16) responded similarly to the bLR saline (bLR-Saline, n=10) group on all measures of goal-tracking behavior on session 8, whereas bHRs treated with flupenthixol (bHR-Flu, n=22) differed significantly from the bHR saline (bHR-Saline, n=10) group on session 8 (*P<0.01, saline vs. flupenthixol). Thus, bLRs learned the CS-US association that produced a goal-tracking CR even though the drug prevented the expression of this behavior during training. Parenthetically, bHRs treated with flupenthixol did not develop a goal-tracking CR.