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Research Articles, Behavioral/Cognitive

Increasing Central Serotonin with 5-hydroxytryptophan Disrupts the Inhibition of Social Gaze in Nonhuman Primates

Hannah B. Weinberg-Wolf, Nick Fagan, Olga Dal Monte and Steve W. C. Chang
Journal of Neuroscience 26 January 2022, 42 (4) 670-681; DOI: https://doi.org/10.1523/JNEUROSCI.0413-21.2021
Hannah B. Weinberg-Wolf
1Department of Psychology, Yale University, New Haven, Connecticut 06520
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Nick Fagan
1Department of Psychology, Yale University, New Haven, Connecticut 06520
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Olga Dal Monte
1Department of Psychology, Yale University, New Haven, Connecticut 06520
2Department of Psychology, University of Turin, 10124 Turin, Italy
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Steve W. C. Chang
1Department of Psychology, Yale University, New Haven, Connecticut 06520
3Department of Neuroscience, Yale University School of Medicine, New Haven, Connecticut 06510
4Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, Connecticut 06510
5Wu Tsai Institute, Yale University, New Haven, Connecticut 06510
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    Figure 1.

    Behavioral task and CSF concentrations of 5-HTP and serotonin following 5-HTP and saline administrations. A, Behavioral task sequence. Example face and luminance-matched scrambled control images are shown on the right. The target image appeared either at the right or left of the instructional cue (see above, Materials and Methods). B, Left, CSF concentration of 5-HTP illustrating the central concentration of 5-HTP after intramuscular injection of saline (blue) or 20 mg/kg 5-HTP (green). Right, CSF concentration of serotonin illustrating the central concentration of serotonin after intramuscular injection of saline (blue) or 20 mg/kg 5-HTP (green). The average CSF concentration per condition is represented by a colored line, and shorter gray lines represent SE. Each shape represents data for individual monkeys. **p < 0.01, t test. C, Quantifications of saccade kinematics during successful orient trials to faces (left) and control images (right) during both 5-HTP (blue) and saline (green) sessions. D, Fixation density heat maps (normalized fixation frequency) of correct orient and inhibit trials for 5-HTP and saline conditions. Black outlines represent the stimuli (central instructional cue and left or right target image).

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    Figure 2.

    5-HTP disrupts orienting and inhibition performance. A, Average performance over the course of a session during orienting trials (top) and inhibition trials (bottom) for face images. B, Average performance over the course of a session during orienting trials (top) and inhibition trials (bottom) for scrambled control images. Performance during saline sessions is shown in blue, whereas 5-HTP session is shown in green (mean ± SEM; A, B). The gray circles above each time series represent significant differences between 5-HTP and saline at each time point (p < 0.05, Wilcoxon signed rank; A, B). C, The percent change in performance because of 5-HTP relative to saline (mean ± SEM), illustrating that 5-HTP selectively impaired performance on inhibition trials with face images (solid lines) but not those with control images (dashed line). ***p < 0.001; n.s., not significant, ANOVA. Inset, Each shape represents data from individual monkeys; filled shapes depict performance on trials with face images, and open shapes depict performance on trials with control images.

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    Figure 3.

    5-HTP reduces flexibility in orienting and inhibiting gaze responses in monkeys. 5-HTP impaired performance when the preceding trials were a switch from the current trial type, but not when they were the same trial type (error bars indicate mean ± SEM); *p < 0.05, Tukey's test. Trial order is shown as a sequence of response types (O or I). For example, I→O indicates the current orientation trial followed a successfully completed inhibition trial in the previous trial. Similarly, O→O→I indicates the current inhibition trial followed a sequence of two successfully completed orientation trials. Each shape represents data from individual monkeys.

  • Figure 4.
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    Figure 4.

    5-HTP increases intertrial initiation time, constricts the pupil, and increases reaction time with concomitant changes in performance. A, Left, 5-HTP increased the amount of time monkeys took before initiating a trial (mean ± SEM; individual session data are overlaid with data from each monkey using different shapes). Right, The percent changes in the intertrial initiation time were correlated with the percent changes in performance because of 5-HTP. B, Left, 5-HTP constricted the pupil (same format as in A, left). Right, The percent changes in pupil constriction were correlated with the percent changes in performance because of 5-HTP. C, Left, 5-HTP increased reaction time (same format as in A, left). Right, The percent changes in reaction time were correlated with the percent changes in orientation trial performance because of 5-HTP. Saline sessions are shown in blue, whereas 5-HTP sessions are shown in green. Each shape represents data from individual monkeys. *p < 0.05, ***p < 0.001, t test. The green lines in the scatter plots (A–C) illustrate linear regression fits.

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The Journal of Neuroscience: 42 (4)
Journal of Neuroscience
Vol. 42, Issue 4
26 Jan 2022
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Increasing Central Serotonin with 5-hydroxytryptophan Disrupts the Inhibition of Social Gaze in Nonhuman Primates
Hannah B. Weinberg-Wolf, Nick Fagan, Olga Dal Monte, Steve W. C. Chang
Journal of Neuroscience 26 January 2022, 42 (4) 670-681; DOI: 10.1523/JNEUROSCI.0413-21.2021

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Increasing Central Serotonin with 5-hydroxytryptophan Disrupts the Inhibition of Social Gaze in Nonhuman Primates
Hannah B. Weinberg-Wolf, Nick Fagan, Olga Dal Monte, Steve W. C. Chang
Journal of Neuroscience 26 January 2022, 42 (4) 670-681; DOI: 10.1523/JNEUROSCI.0413-21.2021
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Keywords

  • 5-HTP
  • causal impairment
  • gaze inhibition
  • gaze orientation
  • nonhuman primates
  • serotonin

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