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. 2024 Apr 22;11(4):ENEURO.0085-24.2024.
doi: 10.1523/ENEURO.0085-24.2024. Print 2024 Apr.

Pharmacological Inhibition of the Nucleus Accumbens Increases Dyadic Social Interaction in Macaques

Hannah F Waguespack  1   2 , Jessica T Jacobs  1   2 , Janis Park  2 , Carolina Campos-Rodriguez  2 , Rafael S Maior  2   3 , Patrick A Forcelli  4   2   5 , Ludise Malkova  4   2
Affiliations

Pharmacological Inhibition of the Nucleus Accumbens Increases Dyadic Social Interaction in Macaques

Hannah F Waguespack et al. eNeuro. .

Abstract

The nucleus accumbens (NAc) is a central component of the brain circuitry that mediates motivated behavior, including reward processing. Since the rewarding properties of social stimuli have a vital role in guiding behavior (both in humans and nonhuman animals), the NAc is likely to contribute to the brain circuitry controlling social behavior. In rodents, prior studies have found that focal pharmacological inhibition of NAc and/or elevation of dopamine in NAc increases social interactions. However, the role of the NAc in social behavior in nonhuman primates remains unknown. We measured the social behavior of eight dyads of male macaques following (1) pharmacological inhibition of the NAc using the GABAA agonist muscimol and (2) focal application of quinpirole, an agonist at the D2 family of dopamine receptors. Transient inhibition of the NAc with muscimol increased social behavior when drug was infused in submissive, but not dominant partners of the dyad. Focal application of quinpirole was without effect on social behavior when infused into the NAc of either dominant or submissive subjects. Our data demonstrate that the NAc contributes to social interactions in nonhuman primates.

Keywords: GABA; dominance; dopamine; muscimol; quinpirole.

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Conflict of interest statement

The authors declare no competing financial interests.

Figures

Figure 1.
Figure 1.
Structural MRIs showing targeting within the NAc for each infused subject. Preinfusion scans are shown for all subjects. Postinfusion scans were conducted for MK, ME, and PP^. In addition, a postmortem 7T scan was conducted on PP^. Red dotted lines show estimated coordinates for each subject on the preinfusion scan. Red ^ indicate cannula tips in the post-infusion and postmortem scans. There was signal dropoff in the left hemisphere of PP^ postmortem scan due to brain placement in the coil. The two lateral cannula tracks in the left hemisphere are the dorsal aspect of infusions aimed for the temporal cortex and amygdala. In most subjects, minimal damage occurred. Atlas plane (+21 mm from interaural plane) from the NIH Laboratory of Neuropsychology “Red” Macaque atlas with red X marks indicated plotted/estimated infusion tips from MRIs.
Figure 2.
Figure 2.
Effect of muscimol (MUS) and quinpirole (QUIN) infusion into the NAc on social contact in dominant and submissive animals. A, Muscimol increases social contact in submissive animals (p = 0.047). B, Neither muscimol nor quinpirole alter social contact in dominant subjects (p = 0.444 and p = 0.999, respectively). C, Differences (and 95% confidence intervals) in estimated marginal means (log transformed) for the two treatment groups within the submissive injected subjects. D, Differences (and 95% confidence intervals) in estimated marginal means (log transformed) for the two treatment groups within the dominant injected subjects. Plots provide a graphical estimation of effect size. Bars in A and B show mean + SEM. Individual data points show the average across infusions for the infused subject in each dyad. *p < 0.05, Sidak corrected; treated versus saline.
Figure 3.
Figure 3.
Effect of muscimol (MUS) and quinpirole (QUIN) infusion into the NAc on grooming in dominant and submissive animals. A, Muscimol increases grooming-related behaviors in submissive subjects (p = 0.030). B, Neither muscimol nor quinpirole alter grooming-related behavior in dominant subjects (p = 0.999 and p = 0.953, respectively). C, Differences (and 95% confidence intervals) in estimated marginal means (log transformed) for the two treatment groups within the submissive injected subjects. D, Differences (and 95% confidence intervals) in estimated marginal means (log transformed) for the two treatment groups within the dominant injected subjects. Plots provide a graphical estimation of effect size. Bars in A and B show mean + SEM. Individual data points show the average across infusions for the infused subject in each dyad. *p < 0.05, Sidak corrected; treated versus saline.
Figure 4.
Figure 4.
Effect of muscimol (MUS) and quinpirole (QUIN) infusion into the NAc on self-directed behavior in dominant and submissive animals. A, Infusion of quinpirole into the NAc increases self-directed behavior in submissive subjects (p = 0.019). B, Neither muscimol nor quinpirole infusion into the NAc alters self-directed behavior in dominant subjects (p = 0.805 and p = 0.969, respectively). C, Differences (and 95% confidence intervals) in estimated marginal means (log transformed) for the two treatment groups within the submissive injected subjects. D, Differences (and 95% confidence intervals) in estimated marginal means (log transformed) for the two treatment groups within the dominant injected subjects. Plots provide a graphical estimation of effect size. Bars in A and B show mean + SEM. Individual data points show the average across infusions for the infused subject in each dyad. *p < 0.05, Sidak corrected; treated versus Saline.
Figure 5.
Figure 5.
Effect of muscimol (MUS) and quinpirole (QUIN) infusion into the NAc on locomotion in dominant and submissive animals. A, Muscimol infused into the NAc decreases locomotion in submissive subjects (p = 0.033). B, Neither muscimol nor quinpirole infused into the NAc alters locomotion in dominant subjects (p = 0.853 and p = 0.480, respectively). C, Differences (and 95% confidence intervals) in estimated marginal means (log transformed) for the two treatment groups within the submissive injected subjects. D, Differences (and 95% confidence intervals) in estimated marginal means (log transformed) for the two treatment groups within the dominant injected subjects. Plots provide a graphical estimation of effect size. Bars in A and B show mean + SEM. Individual data points show the average across infusions for the infused subject in each dyad. *p < 0.05, Sidak corrected; treated versus saline.
Figure 6.
Figure 6.
Effect of muscimol (MUS) and quinpirole (QUIN) infusion into the NAc on manipulation in dominant and submissive animals. A, B, Neither muscimol nor quinpirole alters manipulation in submissive or dominant subjects alone (MUS Dom, p = 0.245; QUIN Dom, p = 0.124; MUS Sub, p = 0.948; QUIN Sub, p = 0.238). C, Differences (and 95% confidence intervals) in estimated marginal means (log transformed) for the two treatment groups within the submissive injected subjects. D, Differences (and 95% confidence intervals) in estimated marginal means (log transformed) for the two treatment groups within the dominant injected subjects. Plots provide a graphical estimation of effect size. Bars in A and B show mean + SEM. Individual data points show the average across infusions for the infused subject in each dyad. *p < 0.05, Sidak corrected; treated versus saline.
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