Dopamine efflux in the nucleus accumbens during within-session extinction, outcome-dependent, and habit-based instrumental responding for food reward

Abstract

Rationale: Dopamine (DA) activity in the nucleus accumbens (NAc) is related to the general motivational effects of rewarding stimuli. Dickinson and colleagues have shown that initial acquisition of instrumental responding reflects action-outcome relationships based on instrumental incentive learning, which establishes the value of an outcome. Given that the sensitivity of responding to outcome devaluation is not affected by NAc lesions, it is unlikely that incentive learning during the action-outcome phase is mediated by DA activity in the NAc.

Objectives: DA efflux in the NAc after limited and extended training was compared on the assumption that comparable changes would be observed during both action-outcome- and habit-based phases of instrumental responding for food. This study also tested the hypothesis that increase in NAc DA activity is correlated with instrumental responding during extinction maintained by a conditioned stimulus paired with food.

Methods: Rats were trained to lever press for food (random-interval 30 s schedule). On the 5th and 16th day of training, microdialysis samples were collected from the NAc or mediodorsal striatum (a control site for generalized activity) during instrumental responding in extinction and then for food reward, and analyzed for DA content using high performance liquid chromatography.

Results: Increase in DA efflux in the NAc accompanied responding for food pellets on both days 5 and 16, with the magnitude of increase significantly enhanced on day 16. DA efflux was also significantly elevated during responding in extinction only on day 16.

Conclusions: These results support a role for NAc DA activity in Pavlovian, but not instrumental, incentive learning.

Fig. 1

Change in DA efflux in the NAc (line graph) during instrumental conditioning on day 5 (left panel) and day 16 (right panel) in the same group of rats (n=8). Dotted lines highlight the Reward phase in which food pellets were delivered on a RI 30-s schedule (times 5–7). Lever presses (gray bars) and magazine entries (black bars) are shown per 10 min bin. Data are represented as mean±SEM. * indicates significant difference from the final baseline value (time 4) according to Dunnett’s method of multiple comparisons, p<0.05. † indicates significant difference from the corresponding data point on day 5 according to a paired t test, p<0.05

Fig. 2

Instrumental performance of rats in the NAc or MD striatal group over 16 training sessions. Rats were trained to lever press for food pellets on a RI 2-s schedule the first day, RI 5-s the next day, and then RI 30-s for the remainder of the study. Each training session terminated upon delivery of 30 pellets (exception: *60 pellets delivered on days before test). Test days (day 5 and 16) were composed of two phases, Extinction and Reward, which lasted 30 min each. Lever presses (gray and striped bars) and magazine entries (black bars) are shown per training session. Data are represented as mean+ SEM

Fig. 3

Change in DA efflux in the NAc (line graph) during instrumental conditioning on day 5 (left panel) and day 16 (right panel) in the same group of rats (n=8). Dotted lines highlight the Extinction phase during which an auditory CS+ was activated on an RI 30-s schedule in the absence of food pellet rewards (times 5–7) and a Reward phase in which food pellets were delivered on a RI 30-s schedule (times 11–13). P represents the period during which five priming pellets were delivered noncontingently. Lever presses (gray bars) and magazine entries (black bars) are shown per 10 min bin. Data are represented as mean±SEM. * Indicates significant difference from the final baseline value (time 4) according to Dunnett’s method of multiple comparisons, p<0.05. † Indicates significant difference from the corresponding data point on day 5 according to a paired ttest, p<0.05. § Indicates significant difference from the final baseline value (time 4; ttest, p<0.05)

Fig. 4

Change in DA efflux in the MD striatum (line graph) during instrumental conditioning on day 5 (left panel) and day 16 (right panel) in the same group of rats (n=6). See Fig. 3 for explanation of symbols. No statistically significant results were observed for neurochemical data set. † Indicates significant difference from the corresponding behavioral score on day 5 according to a paired ttest, p<0.05

Fig. 5

Correlation between instrumental response rates and NAc DA efflux. Scatter plot of lever presses/10 min (y-axis) and corresponding percent change in DA efflux (x-axis) for data obtained on day 5 (left panel) and day 6 (right panel). Shown on each graph is the best fit linear regression line and R² value

Fig. 6

Location of microdialysis probes in the NAc and MD striatum. Black bars represent 2 mm length of dialysis membranes. Numbers beside each plate correspond to millimeter from bregma. Coronal drawings were modified from Paxinos and Watson (1997)