Encoding of aversion by dopamine and the nucleus accumbens

Abstract

Adaptive motivated behavior requires rapid discrimination between beneficial and harmful stimuli. Such discrimination leads to the generation of either an approach or rejection response, as appropriate, and enables organisms to maximize reward and minimize punishment. Classically, the nucleus accumbens (NAc) and the dopamine projection to it are considered an integral part of the brain's reward circuit, i.e., they direct approach and consumption behaviors and underlie positive reinforcement. This reward-centered framing ignores important evidence about the role of this system in encoding aversive events. One reason for bias toward reward is the difficulty in designing experiments in which animals repeatedly experience punishments; another is the challenge in dissociating the response to an aversive stimulus itself from the reward/relief experienced when an aversive stimulus is terminated. Here, we review studies that employ techniques with sufficient time resolution to measure responses in ventral tegmental area and NAc to aversive stimuli as they are delivered. We also present novel findings showing that the same stimulus - intra-oral infusion of sucrose - has differing effects on NAc shell dopamine release depending on the prior experience. Here, for some rats, sucrose was rendered aversive by explicitly pairing it with malaise in a conditioned taste aversion paradigm. Thereafter, sucrose infusions led to a suppression of dopamine with a similar magnitude and time course to intra-oral infusions of a bitter quinine solution. The results are discussed in the context of regional differences in dopamine signaling and the implications of a pause in phasic dopamine release within the NAc shell. Together with our data, the emerging literature suggests an important role for differential phasic dopamine signaling in aversion vs. reward.

Keywords: conditioned taste aversion; electrophysiology; reward; taste reactivity; ventral tegmental area; voltammetry.

Figure 1

Opposing effects of aversive and rewarding taste stimuli on dopamine release in NAc shell. Representative trial examples resulting from intra-oral infusions of (A) quinine in naïve rats, (B) sucrose in rats that had experienced sucrose explicitly paired with LiCl-induced malaise, and (C) sucrose in rats that did not have sucrose paired with malaise. Color plots (top panels) show changes in current (color) at different electrode potentials (y-axis) over time (x-axis). Dopamine is distinguished by its characteristic oxidation peak (∼0.6 V; black triangle; green/purple feature). Dopamine concentration traces (lower panels) are extracted from above using principal component analysis. Horizontal bars and dashed vertical lines indicate time of infusion.

Figure 2

Aversive stimuli suppress dopamine release in NAc shell. Averaged dopamine concentration traces showing suppression of dopamine release after quinine (A) and sucrose infusions in Paired rats [(B), red trace] and no change in dopamine release in Unpaired rats [(B), blue trace]. *p < 0.05 pre-infusion vs. infusion epoch.

Figure 3

Induction of conditioned taste aversion leads to a decrease in the palatability of sucrose. In Paired rats, sucrose infusions evoke more negative and less positive orofacial movements than in Unpaired rats. *p < 0.05 vs. Paired rats.