Dopamine Signals Evolve During Learning to Avoid Harm

A new study from Northwestern University has provided insight into how dopamine, a neurotransmitter often associated with reward, also plays a critical role in helping animals avoid harm. The research, conducted in mice, reveals how dopamine signals evolve over time to support learning from negative outcomes.

While it is well established that dopamine activity increases in response to pleasurable stimuli, this study is among the first to track how dopamine signals change during the learning process of avoiding negative experiences. The findings, published April 22 in Current Biology, show that two regions of the nucleus accumbens respond differently to aversive situations, depending on how predictable or controllable the experience is.

Learning to avoid negative outcomes

In the experiment, researchers trained mice to respond to a five-second warning cue that predicted an aversive event. If the mice moved to the opposite side of a two-chamber box during the cue, they could avoid the event. As the mice became proficient at this avoidance behavior, researchers recorded dopamine activity in two subregions of the nucleus accumbens – the ventromedial shell and the core.

In the ventromedial shell, dopamine levels initially spiked in response to the negative event. Over time, as mice learned to associate the cue with the aversive outcome, the dopamine surge shifted from the event to the cue. Eventually, this dopamine response diminished as the mice consistently avoided the event.

In contrast, dopamine levels in the core decreased in response to both the cue and the event. The reduction in dopamine during the cue phase intensified with training, particularly as the animals improved their avoidance behavior.

Dopamine signals reflect learning stage and context

These findings suggest that the ventromedial shell may support early learning by highlighting salient negative events, while the core helps consolidate later learning by reinforcing successful avoidance strategies. When researchers altered the conditions so the mice could no longer avoid the negative outcome, the dopamine signals returned to patterns seen during early training. 

“This shows that the dopamine signals are flexible, sensitive to task rules, and may help us adapt to changes in the environment,” Gabriela Lopez said. 

Implications for mental health research

The authors noted that these findings offer clues into why individuals may differ in their ability to learn from negative experiences. More broadly, the research provides a possible mechanism for how excessive avoidance – a feature of several psychiatric disorders such as anxiety, obsessive-compulsive disorder and depression – could develop. Altered dopamine signaling may lead to an exaggerated perception of threat, limiting an individual’s willingness to engage in normal activities.

The study also addresses recent public interest in “dopamine detox” practices. Proponents of these approaches suggest that avoiding pleasurable stimuli, such as social media or processed foods, can reset the brain’s reward system. However, the findings highlight that dopamine is not exclusively linked to pleasure but is essential for adaptive learning across a range of experiences, both good and bad.

Reference: Lopez GC, Van Camp LD, Kovaleski RF, et al. Region-specific nucleus accumbens dopamine signals encode distinct aspects of avoidance learning. Current Biology. doi: 10.1016/j.cub.2025.04.006

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