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Research ArticleResearch Article: New Research, Cognition and Behavior

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

Hannah F. Waguespack, Jessica T. Jacobs, Janis Park, Carolina Campos-Rodriguez, Rafael S. Maior, Patrick A. Forcelli and Ludise Malkova
eNeuro 4 April 2024, 11 (4) ENEURO.0085-24.2024; https://doi.org/10.1523/ENEURO.0085-24.2024
Hannah F. Waguespack
1Interdisciplinary Program in Neuroscience, Georgetown University, Washington, DC 20007
2Department of Pharmacology & Physiology, Georgetown University, Washington, DC 20007
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Jessica T. Jacobs
1Interdisciplinary Program in Neuroscience, Georgetown University, Washington, DC 20007
2Department of Pharmacology & Physiology, Georgetown University, Washington, DC 20007
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Janis Park
2Department of Pharmacology & Physiology, Georgetown University, Washington, DC 20007
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Carolina Campos-Rodriguez
2Department of Pharmacology & Physiology, Georgetown University, Washington, DC 20007
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Rafael S. Maior
2Department of Pharmacology & Physiology, Georgetown University, Washington, DC 20007
3Laboratory of Neurosciences and Behavior, Department of Physiological Sciences, Institute of Biology, University of Brasilia, Brasilia 70.910-900, Brazil
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Patrick A. Forcelli
1Interdisciplinary Program in Neuroscience, Georgetown University, Washington, DC 20007
2Department of Pharmacology & Physiology, Georgetown University, Washington, DC 20007
4Department of Neuroscience, Georgetown University, Washington, DC 20007
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Ludise Malkova
1Interdisciplinary Program in Neuroscience, Georgetown University, Washington, DC 20007
2Department of Pharmacology & Physiology, Georgetown University, Washington, DC 20007
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  • Figure 1.
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    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.
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    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.

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    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.

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    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.

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    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.

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    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.

Tables

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    Table 1.

    Operational definitions of general (nonsocial) and social behaviors observed in these experiments

    BehaviorDescription
    General (nonsocial)
     LocomotionWalks, runs, climbs, or jumps
     ManipulationHandles, chews, licks, moves, or smells objects or cage parts
     PassiveInactive, stays in one location
     Self-directedEngages in self-directed behaviors, i.e., self-grooms, hugs head, self-grabs and bites, presses face with hands, self-holds, closes fists, self-clutches, sexually self-stimulates, prone, or head on chest
    Social
     ApproachInitiates social contact; moves body or head toward the conspecific
     IsolationSits alone
     Social contactAny physical contact between the subject and conspecific.
     Grooming-related behaviors conspecificSubject grooms the conspecific, subject presents for grooming, subject is groomed by the conspecific
    • Note that our analysis ethogram also included aggression, mounting, play, withdrawal, motor stereotypies, and vocalizations, but these were either completely absent or observed at very low rates so were not formally analyzed further.

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    Table 2.

    Table showing dyads, dominant subjects in each dyad, and the number of infusions per subject in a dyad

    Infused subjectME ○PP □PP^ ΔFR ∇MK ◊FI ⎔JO ⊗BA ⊠
    PartnerPPMEME^MKFRFRHXCB
    DominantMEMEME^FRFRFRJOBA
    SAL42333324
    MUS42242233
    QUIN43332123
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    Table 3.

    Statistical table

    Manuscript referenceFigureData structureType of testMultiple comparisons correctionDifference in estimated marginal means and 95% confidence intervals
    aFig. 2A,CLog-normalMixed effects modelSidak

    SAL v. MUS: 0.375 [0.004, 0.746]

    SAL v. QUIN: −0.0630 [−0.414, 0.353]

    bFig. 2B,DLog-normalMixed effects modelSidak

    SAL v. MUS: −0.162 [−0.486, 0.161]

    SAL v. QUIN: −0.006 [0.746, 0.353]

    cFig. 3A,CLog-normalMixed effects modelSidak

    SAL v. MUS: 0.784 [0.066, 1.502]

    SAL v. QUIN: 0.392 [−0.342, 1.126]

    dFig. 3B,DLog-normalMixed effects modelSidak

    SAL v. MUS: 0.010 [−0.617, 0.638]

    SAL v. QUIN: −0.076 [−0.710, 0.558]

    eFig. 4A,CLog-normalMixed effects modelSidak

    SAL v. MUS: 0.246 [−0.207, 0.700]

    SAL v. QUIN: 0.562 [0.081, 1.044]

    fFig. 4B,DLog-normalMixed effects modelSidak

    SAL v. MUS: −0.100 [−0.490, 0.291]

    SAL v. QUIN: −0.039 [−0.440, 0.362]

    gFig. 5A,CLog-normalMixed effects modelSidak

    SAL v. MUS: −0.444 [−0.858, −0.031]

    SAL v. QUIN: 0.049 [−0.362, 0.461]

    hFig. 5B,DLog-normalMixed effects modelSidak

    SAL v. MUS: 0.077 [−0.280, 0.434]

    SAL v. QUIN: 0.168 [−0.189, 0.526]

    iFig. 6A,CLog-normalMixed effects modelSidak

    SAL v. MUS: −0.076 [−0.168, 0.835]

    SAL v. QUIN: 0.062 [−0.093, 0.957]

    jFig. 6B,DLog-normalMixed effects modelSidak

    SAL v. MUS: −0.076 [−0.673, 0.521]

    SAL v. QUIN: 0.432 [−0.211, 1.075]

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Pharmacological Inhibition of the Nucleus Accumbens Increases Dyadic Social Interaction in Macaques
Hannah F. Waguespack, Jessica T. Jacobs, Janis Park, Carolina Campos-Rodriguez, Rafael S. Maior, Patrick A. Forcelli, Ludise Malkova
eNeuro 4 April 2024, 11 (4) ENEURO.0085-24.2024; DOI: 10.1523/ENEURO.0085-24.2024

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Pharmacological Inhibition of the Nucleus Accumbens Increases Dyadic Social Interaction in Macaques
Hannah F. Waguespack, Jessica T. Jacobs, Janis Park, Carolina Campos-Rodriguez, Rafael S. Maior, Patrick A. Forcelli, Ludise Malkova
eNeuro 4 April 2024, 11 (4) ENEURO.0085-24.2024; DOI: 10.1523/ENEURO.0085-24.2024
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Keywords

  • dominance
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  • quinpirole

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