Phasic dopamine release in the rat nucleus accumbens predicts approach and avoidance performance

Abstract

Dopamine (DA) is critical for reward processing, but significantly less is known about its role in punishment avoidance. Using a combined approach-avoidance task, we measured phasic DA release in the nucleus accumbens (NAc) of rats during presentation of cues that predicted reward, punishment or neutral outcomes and investigated individual differences based on avoidance performance. Here we show that DA release within a single microenvironment is higher for reward and avoidance cues compared with neutral cues and positively correlated with poor avoidance behaviour. We found that DA release delineates trial-type during sessions with good avoidance but is non-selective during poor avoidance, with high release correlating with poor performance. These data demonstrate that phasic DA is released during cued approach and avoidance within the same microenvironment and abnormal processing of value signals is correlated with poor performance.

Figure 1. Task design and population behavioural results (N=10 rats; 18 sessions).

Sessions consisted of 3 trial types: reward (a), neutral (b), and shock (c), which could be identified by their unique auditory cue. (a–c) At the beginning of each trial, rats were presented with a light cue and trial-specific sound cue 5s before lever extension and then had a maximum of 10 s to press the lever before it was retracted. If rats pressed the lever, they could receive a sucrose pellet reward, avoid an impending foot shock (0.42 mV), or experience no consequence, depending on the identity of the sound cue. If rats failed to press the lever within 10 s after its extension into the chamber, they would alternatively receive no sucrose reward, receive continuous foot shock (0.42 mV), or experience no consequence depending on the identity of the sound cue. Once shock commenced, it could be terminated by lever press. After each consequence, the trial progressed into a 20s ITI. Trial types were pseudo-randomly interleaved within each session (∼60 min) and sound cue identity was counterbalanced across rats. (d,e) Percent lever press and reaction time computed across each session (d) and across rats (e). Bars with asterisks represent significance (T-test; p<0.05; n=18 for (d) and n=10 for (e)). Error bars represent s.e.m. (f) Correlation between percentage lever press and reaction time to press for each trial type (reward, neutral, and shock) across all sessions (g) Placement of chronic recording electrodes within the NAc core based on histology.

Figure 2. Average dopamine release (N=10 rats) during cue and lever epochs for each trial type.

(a) Dopamine release (nM) across time for reward (blue), neutral (yellow), and shock (red) trials. Dopamine release is baseline (5s before light onset to light onset) subtracted. (b–e) Quantification of DA release for press and non-press responses during the cue epoch (cue onset to lever extension; 5s) and lever epoch (lever extension plus 1s). Bars with asterisks represent significance (T-test; P<0.05). Error bars represent s.e.m. (f,g) Correlation between shock and reward trials normalized over neutral trials (shock minus neutral; reward minus neutral) for both cue epoch and lever epoch. (h–m) False-color plots indicate voltammetric current (z-axis) plotted against applied scan potential (y-axis) and time (x-axis) for representative press trials aligned to cue onset for each of the three trial types (h–j; Reward, Neutral, and Shock), as well as averaged press trials aligned to cue onset for each of the three trial types (k–m; Average Reward, Average Neutral, Average Shock). Insets show cyclic voltammogram for dopamine; scale bars are set to 0.7 nA for individual examples and 0.4 nA for averages.

Figure 3. Correlation of DA release with behavioural measures.

Each dot represents an individual session; all recording sessions are represented. (a–d) DA release is not significantly correlated with lever press or reaction time for reward trials (blue). (e,f, i,j) DA release is negatively correlated with lever press and positively correlated with reaction time for both neutral (yellow) and shock (red) trials during the cue epoch. (g,h) DA release is negatively correlated with lever press and positively correlated with reaction time for neutral trials in the lever epoch. (k,l) DA is not significantly correlated with behavioural measures for shock trials during the lever epoch.

Figure 4. Poor and good avoidance exhibit differences in behaviour and dopamine release across trial types.

Reward, neutral, and shock trial types are represented by blue, yellow, and red, respectively. Behavioural differences are shown using percent lever press (a) and reaction times (b) for poor avoidance and percent lever press (c) and reaction times (d) for good avoiders. Bars with asterisks represent significance (T-test; P<0.05; n=6 rats for good avoidance, 5 rats for poor avoidance). Error bars represent s.e.m. (e–h) Dopamine quantification for poor and good avoiders. Dopamine release (nM) for each trial type is shown across time with cue and lever epochs indicated for poor (e) and good avoiders (g), respectively. Dopamine release is quantified during the cue epoch for each trial type for poor (f) and good (h) avoiders. Error bars represent s.e.m. (i–k) Analysis of stress-related behaviours during press and failed press. Percent freezing (i), orienting to the lever (j), and rearing (k) during poor and good avoidance. Asterisks indicate P<0.05 in chi-square; n=6 rats.