A Transient Dopamine Signal Represents Avoidance Value and Causally Influences the Demand to Avoid.

While an extensive literature supports the notion that mesocorticolimbic dopamine plays a role in negative reinforcement, recent evidence suggests that dopamine exclusively encodes the value of positive reinforcement. In the present study, we employed a behavioral economics approach to investigate whether dopamine plays a role in the valuation of negative reinforcement. Using rats as subjects, we first applied fast-scan cyclic voltammetry (FSCV) to determine that dopamine concentration decreases with the number of lever presses required to avoid electrical footshock (i.e., the economic price of avoidance). Analysis of the rate of decay of avoidance demand curves, which depict an inverse relationship between avoidance and increasing price, allows for inference of the worth an animal places on avoidance outcomes. Rapidly decaying demand curves indicate increased price sensitivity, or low worth placed on avoidance outcomes, while slow rates of decay indicate reduced price sensitivity, or greater worth placed on avoidance outcomes. We therefore used optogenetics to assess how inducing dopamine release causally modifies the demand to avoid electrical footshock in an economic setting. Increasing release at an avoidance predictive cue made animals more sensitive to price, consistent with a negative reward prediction error (i.e., the animal perceives they received a worse outcome than expected). Increasing release at avoidance made animals less sensitive to price, consistent with a positive reward prediction error (i.e., the animal perceives they received a better outcome than expected). These data demonstrate that transient dopamine release events represent the value of avoidance outcomes and can predictably modify the demand to avoid.

Diazepam Concurrently Increases the Frequency and Decreases the Amplitude of Transient Dopamine Release Events in the Nucleus Accumbens.

Benzodiazepines are commonly prescribed anxiolytics that pose abuse liability in susceptible individuals. Although it is well established that all drugs of abuse increase brain dopamine levels, and benzodiazepines are allosteric modulators of the GABAA receptor, it remains unclear how they alter dopamine release. Using in vivo fast-scan cyclic voltammetry, we measured diazepam-induced changes in the frequency and amplitude of transient dopamine release events. We found that diazepam concurrently increases the frequency and decreases the amplitude of transient dopamine release events in the awake and freely moving rat. The time course during which diazepam altered the frequency and amplitude of dopamine release events diverged, with the decreased amplitude effect being shorter lived than the increase in frequency, but both showing similar rates of onset. We conclude that diazepam increases the frequency of accumbal dopamine release events by disinhibiting dopamine neurons, but also decreases their amplitude. We speculate that the modest abuse liability of benzodiazepines is due to their ability to decrease the amplitude of dopamine release events in addition to increasing their frequency.

A transient dopamine signal encodes subjective value and causally influences demand in an economic context.

The mesolimbic dopamine system is strongly implicated in motivational processes. Currently accepted theories suggest that transient mesolimbic dopamine release events energize reward seeking and encode reward value. During the pursuit of reward, critical associations are formed between the reward and cues that predict its availability. Conditioned by these experiences, dopamine neurons begin to fire upon the earliest presentation of a cue, and again at the receipt of reward. The resulting dopamine concentration scales proportionally to the value of the reward. In this study, we used a behavioral economics approach to quantify how transient dopamine release events scale with price and causally alter price sensitivity. We presented sucrose to rats across a range of prices and modeled the resulting demand curves to estimate price sensitivity. Using fast-scan cyclic voltammetry, we determined that the concentration of accumbal dopamine time-locked to cue presentation decreased with price. These data confirm and extend the notion that dopamine release events originating in the ventral tegmental area encode subjective value. Using optogenetics to augment dopamine concentration, we found that enhancing dopamine release at cue made demand more sensitive to price and decreased dopamine concentration at reward delivery. From these observations, we infer that value is decreased because of a negative reward prediction error (i.e., the animal receives less than expected). Conversely, enhancing dopamine at reward made demand less sensitive to price. We attribute this finding to a positive reward prediction error, whereby the animal perceives they received a better value than anticipated.