biostudies-literatureEshel NNIDA NIH HHSNIMH NIH HHS500-514.e5https://www.ebi.ac.uk/biostudies/studies/S-EPMC10922131biostudies-literatureUnknown112(3)Striatal dopamine (DA) release has long been linked to reward processing, but it remains controversial whether DA release reflects costs or benefits and how these signals vary with motivation. Here, we measure DA release in the nucleus accumbens (NAc) and dorsolateral striatum (DLS) while independently varying costs and benefits and apply behavioral economic principles to determine a mouse's level of motivation. We reveal that DA release in both structures incorporates both reward magnitude and sunk cost. Surprisingly, motivation was inversely correlated with reward-evoked DA release. Furthermore, optogenetically evoked DA release was also heavily dependent on sunk cost. Our results reconcile previous disparate findings by demonstrating that striatal DA release simultaneously encodes cost, benefit, and motivation but in distinct manners over different timescales. Future work will be necessary to determine whether the reduction in phasic DA release in highly motivated animals is due to changes in tonic DA levels.NeuronStriatal dopamine integrates cost, benefit, and motivation.PMC10922131P50 DA042012K08 MH123791Taniguchi LMalenka RCGroome AMOsterman AKBentzley BSShank ANTucciarone JEshel NTouponse GCCardozo Pinto DFWang ARfalseStriatal dopamine integrates cost, benefit, and motivation.Striatal dopamine (DA) release has long been linked to reward processing, but it remains controversial whether DA release reflects costs or benefits and how these signals vary with motivation. Here, we measure DA release in the nucleus accumbens (NAc) and dorsolateral striatum (DLS) while independently varying costs and benefits and apply behavioral economic principles to determine a mouse's level of motivation. We reveal that DA release in both structures incorporates both reward magnitude and sunk cost. Surprisingly, motivation was inversely correlated with reward-evoked DA release. Furthermore, optogenetically evoked DA release was also heavily dependent on sunk cost. Our results reconcile previous disparate findings by demonstrating that striatal DA release simultaneously encodes cost, benefit, and motivation but in distinct manners over different timescales. Future work will be necessary to determine whether the reduction in phasic DA release in highly motivated animals is due to changes in tonic DA levels.2024-01-01T00:00:00Z2024 Feb2025-04-18T12:58:52.309Z2025-04-06T22:27:05.039ZS-EPMC109221313801647110.1016/j.neuron.2023.10.038