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. 2023 May 19;48(12):1821–1831. doi: 10.1038/s41386-023-01604-5

Fig. 3. Systemic DREADD inhibition of mPFC neurons does not affect impulsive choice, however, inhibition of mPFC-NAc projections increases impulsive choice.

Fig. 3

A Impulsive choice (AUC) was not different from baseline following systemic (IP) infusion of either dose of CNO or vehicle (n = 9; P = 0.452). Each dot represents a single subject. B Illustration of rat brain showing transduction of the inhibitory Gi-DREADD virus (hM4Di) in the mPFC and implantation of guide cannula in the NAc for infusion of CNO or vehicle. C Percent of trials in which a rat chose the larger delayed reward across delays during baseline and following intra-NAc vehicle infusion (n = 16). Inset shows no significant difference in DD task performance (measured by AUC) (P = 0.633). D CNO significantly increased impulsive choice across delays (P = 0.003). Planned comparisons showed that intra-NAc CNO did not affect choice of the larger reward when there was no delay (0-s), but significantly reduced large choice on 10-s (P = 0.012) and 20-s delay (P = 0.007). E Similarly, intra-NAc infusion of CNO significantly decreased AUC (P = 0.003). F Intra-NAc CNO infusion in rats not transduced with Gi-DREADD virus had no effect on choice of the larger-delayed reinforcer (P = 0.134). G Scatter plots and fit lines (red) showing correlation between the percent of large choices at baseline (i.e., baseline delay tolerance or choice impulsivity) and the change in percent large choice following CNO infusion for the 5-s (left), 10-s (middle) and 20-s (right) delays. Black lines are the constraints on the positive or negative CNO-mediated change that could occur given the baseline percent large choices. Significant negative correlations were identified for the 10-s (r = −0.57, P = 0.020) and 20-s (r = −0.57, P = 0.028) delays, but not for the 5 s delay (P = 0.288). Greater percent decreases in choice of the large alternative occurred in animals with higher percentage choice of the large alternative, i.e., animals with lower levels of trait choice impulsivity. Error bars indicate +/− SEM. *P ≤ 0.05, **P < 0.01.