A study published on April 23, 2025, identified that distinct dopamine activity patterns exist between two separate regions in the brain reward circuitry during avoidance learning in the nucleus accumbens (NAc). The study’s conclusions reveal important brain mechanisms underlying challenging learning and may offer insight into the molecular bases of anxiety and obsessive behavioural disorders.
Researchers found that opposing dopamine response patterns surface between the NAc core (Core) and ventromedial shell (vmShell) subregions during neuronal processing of electric footshock avoidance tasks. Scientists monitored dopamine activity within the brain throughout an entire week of training to establish the separate learning capacities of these NAc subregions.
During a seven-day training period, mice learned to move across the chamber within five seconds of hearing the warning cue to escape a 0.4 mA footshock. The avoidance technique resulted in successful outcomes during 85.1% of conducted trials by the seventh day. The mice developed a steady decline in their foot-cross response durations, which plateaued at 2.89 seconds on average. Mice learned to identify risk-free periods during safe trial intervals by showing a progressive reduction in freezing behavior, which is usually a fear response.
Scientists measured dopamine activity in the Core and vmShell through real-time recordings using a fluorescent dopamine sensor (dLight1.3b) together with fiber photometry. Core dopamine levels showed a decrease when warning cues appeared initially during training. The warning signal responses, brief decreases in dopamine activity, referred to as “dips,” showed increasing strength mainly in avoidance trial situations in which the mice succeeded.
The vmShell dopamine response was elevated when participants received cues and shocks at first, yet it decreased with each training session. The vmShell-originated responses decreased dramatically after day four, which indicates the vmShell participates in initial threat learning but becomes less active during expert performance.
The research data analysis revealed both significant differences in cue-driven neural activity between brain areas (F₁,₂₀ = 64.78, p < 0.0001) and vital statistical changes across learning sessions (F₃.89, 76.54 = 3.39, p = 0.014). Data analysis through an interaction term revealed separate learning patterns regarding dopamine signal changes between Core and vmShell networks (F₆,₁₁₈ = 10.95, p < 0.0001).
The team studied the differences in dopamine signals that occurred between avoid (no shock) situations and escape (shock before crossing) situations. The warning sign evoked increasingly severe drops in Core dopamine activity in both trial conditions, although these signals diverged from each other approximately 1.85 seconds after the warning on days 5 through 7. A statistically significant F₁,₁₃ = 35.39 difference was detected (p < 0.0001).
During warning cue periods, vmShell dopamine activity remained equivalent between avoid and escape trials but displayed robust activation when subjects received the shock during escape trials. The vmShell shows evidence of directly processing unpleasant sensory experiences, but the Core demonstrates better knowledge of predictive signals and action value computation.
The new decoding approach used by researchers determined how dopamine activity reacted to key behavioral instances, including cues, crossings, and shocks. The research found that the vmShell demonstrated the maximum shock response on day 1, and this responsiveness decreased by day 3 (F₆,₃₆ = 4.88, p < 0.001), validating its proposed role in detecting threatening situations acutely. The Core maintained consistent cue and action encoding behaviors during training sessions (p = 0.437) while refining its neurosignal distinction between avoid and escape trials from day 1 to day 3.
The findings challenge the traditional concept that dopamine exists only for reward learning processes. The evidence demonstrates that the network shows dynamic participation of NAc subregions during avoidance learning because Core cells encode prediction errors to guide learning processes, but vmShell cells highlight initial threat detection.
The researchers reveal how their findings could lead to improved therapeutic methods for treating conditions that show harmful avoidance behaviors like anxiety, OCD, and depression. Scientists can develop strategies to reconfigure these brain circuits by understanding their developmental process, transforming novice into expert behavior patterns.
References: Lopez GC, Van Camp LD, Kovaleski RF, et al. Region-specific nucleus accumbens dopamine signals encode distinct aspects of avoidance learning. Curr Biol. 2025;35(8):eLocator. doi:10.1016/j.cub.2025.04.006
