μ- and δ-opioid-related processes in the accumbens core and shell differentially mediate the influence of reward-guided and stimulus-guided decisions on choice.

Two motivational processes affect choice between actions: (1) changes in the reward value of the goal or outcome of an action and (2) changes in the predicted value of an action based on outcome-related stimuli. Here, we evaluated the role of μ-opioid receptor (MOR) and δ-opioid receptor (DOR) in the nucleus accumbens in the way these motivational processes influence choice using outcome revaluation and pavlovian-instrumental transfer tests. We first examined the effect of genetic deletion of MOR and DOR in specific knock-out mice. We then assessed the effect of infusing the MOR antagonist d-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH(2) (CTAP) or the DOR antagonist naltrindole into the core or shell subregions of the nucleus accumbens on these tests in rats. We found that, whereas MOR knock-outs showed normal transfer, they failed to show a selective outcome revaluation effect. Conversely, DOR knock-outs showed normal revaluation but were insensitive to the influence of outcome-related cues on choice. This double dissociation was also found regionally within the nucleus accumbens in rats. Infusion of naltrindole into the accumbens shell abolished transfer but had no effect on outcome revaluation and did not influence either effect when infused into the accumbens core. Conversely, infusion of CTAP into the accumbens core abolished sensitivity to outcome revaluation but had no effect on transfer and did not influence either effect when infused into the accumbens shell. These results suggest that reward-based and stimulus-based values exert distinct motivational influences on choice that can be doubly dissociated both neuroanatomically and neurochemically at the level of the nucleus accumbens.