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

Abstract

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.

Dopamine signals related to appetitive and aversive events in paradigms that manipulate reward and avoidability

“…The work described above clearly indicates that, at least in good avoiders, cues that predict the ability to avoid shock increase DA to levels associated with cues that predict reward. Recent work has further demonstrated that DA computes the value associated with negative reinforcement by measuring DA release using FSCV during a behavioral economics task where the price to avoid shock increased progressively over the course of a session (Pultorak et al, 2018). They found an inverse relationship between DA amplitude at avoidance-predictive cues and the effort needed in order to avoid.…”

Anhedonia following mild traumatic brain injury in rats: A behavioral economic analysis of positive and negative reinforcement

“…Lesions of dopaminergic terminals and dopaminergic antagonists impair foot shock avoidance, and dopamine release is correlated with avoidance responses. [58][59][60][61][62] TBI modifies neural circuits involving both DLPFC and dopamine systems. [63][64][65][66] While dopaminergic systems have largely been implicated in both positive and negative reinforcement, any mechanistic explanation of our results will have to include differential actions of TBI on avoidance of foot shock, but not escape or positive reinforcement.…”

Frontiers in electrochemical sensors for neurotransmitter detection: towards measuring neurotransmitters as chemical diagnostics for brain disorders

“…DA FSCV technology described above culminated, among other seminal ndings, in establishing DA's major roles in reward and cognition. [107][108][109][110][111][112][113][114][115] These ndings spearheaded an explosion of studies to understand these behaviors in the context of the dopaminergic system. In particular, it was found that the reward-related behaviors described above are controlled by the mesolimbic DA circuits, which are in turn modulated by endogenous factors such as hormones.…”