This article combines microdialysis, voltammetry, and optogenetic methods to study mesolimbic dopamine function in a reward task. The authors conclude that dopamine mediates the motivational value of working for a reward.

Hamid, Pettigrew and colleagues trained rats to work in a novel reward task, somewhat similar to a slot machine, with a left arm and right arm each paying independently. The opportunity to play was signaled by illumination of a middle porthole into which the rat had to put its nose. Then, hearing a ‘go’ cue, the rat could move its nose to either a left hole or a right hole as it chose (each hole corresponded to the two arms of the slot machine: pull whichever arm you think is luckiest). Rats could sample and focus on whichever hole currently giving the best sucrose payout. The winning hole could gradually change and reverse over time, so that the rat had to pay attention to recent success rates in order to track the best hole.

Using microdialysis in the nucleus accumbens, Hamid et al. first found that dopamine levels were highest when the rat had recently been winning high sucrose reward payouts. Using voltammetry to assess faster changes, the authors report that a phasic pulse of dopamine occurred whenever the rat initiated the game, and another occurred at the go cue when it picked left versus right alternatives, and a third pulse occurred when the rat heard a reward cue telling it it had won. However, dopamine dropped when the sucrose pellet was actually received and eaten, indicating that dopamine was not coding the hedonic impact of the reward.

Hamid and colleagues finally gave a 0.5-sec pulse of optogenetic ChR2 stimulation of dopamine neurons in the ventral tegmentum of TH-Cre rats at two different moments to assess the impact on the rats’ behavior. For some, ChR2 stimulation occurred at the beginning of the game when the center porthole was first lit. These rats consequently sped up their approach to initiate the game. Hamid et al. interpreted this as increased dopaminergic motivation to earn a reward. In other trials, the ChR2 laser was instead used later just after the rats had chosen left versus right. These rats consequently tended to repeat their choice of the same side again on the next trial. The authors interpret this as indicating a dopamine-mediated prediction error that reinforced the preceding action.

An alternative interpretation of the left/right ChR2 effect, in terms of incentive salience, might be as follows: just as the early dopamine pulse at game onset primed the motivation for the reward, so the later pulse amplified the motivational incentive salience of that ‘particular choice option’ it was paired with, making that option more attractive at the stimulated moment, and so remembered as more attractive on the next trial. The later pulse did not prime speed on the next trial because that next trial was too temporally distant for priming to last. But the memory of enhancement could last, making the ChR2-paired option more ‘wanted’ next time.

In any case, Hamid and colleagues conclude: “Our interpretation of mesolimbic [DA] as signalling the value of work… It may be best considered as signaling the motivational excitement associated with reward expectation…”. Further, they suggest their interpretation “grounds this motivational aspect of dopamine fluctuations in the quantitative frameworks of machine learning”, connecting motivation and reinforcement views of the role of dopamine in reward.

F1000Prime Recommendations, Dissents and Comments for [Hamid AA et al., Nat Neurosci 2016, 19(1):117-26]. In F1000Prime, 15 Feb 2016;

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Mesolimbic dopamine signals the value of work.

Hamid AA, Pettibone JR, Mabrouk OS, Hetrick VL, Schmidt R, Vander Weele CM, Kennedy RT, Aragona BJ, Berke JD.

Nat Neurosci. 2016 Jan;19(1):117-26. doi: 10.1038/nn.4173.