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Research ArticleResearch Article: New Research, Cognition and Behavior

Ventral Pallidal GABAergic Neurons Drive Consumption in Male, But Not Female, Rats

Alexandra Scott, Anika Paulson, Collin Prill, Klaiten Kermoade, Bailey Newell, Elizabeth A. Eckenwiler, Julia C. Lemos and Jocelyn M. Richard
eNeuro 14 January 2025, 12 (2) ENEURO.0245-24.2025; https://doi.org/10.1523/ENEURO.0245-24.2025
Alexandra Scott
1Graduate Program in Neuroscience, University of Minnesota, Minneapolis, Minnesota
2Medical Discovery Team on Addiction, University of Minnesota, Minneapolis, Minnesota
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Anika Paulson
2Medical Discovery Team on Addiction, University of Minnesota, Minneapolis, Minnesota
3Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota
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Collin Prill
2Medical Discovery Team on Addiction, University of Minnesota, Minneapolis, Minnesota
3Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota
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Klaiten Kermoade
3Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota
4Molecular Pharmacological and Therapeutics, University of Minnesota, Minneapolis, Minnesota
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Bailey Newell
2Medical Discovery Team on Addiction, University of Minnesota, Minneapolis, Minnesota
3Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota
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  • ORCID record for Bailey Newell
Elizabeth A. Eckenwiler
1Graduate Program in Neuroscience, University of Minnesota, Minneapolis, Minnesota
2Medical Discovery Team on Addiction, University of Minnesota, Minneapolis, Minnesota
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Julia C. Lemos
2Medical Discovery Team on Addiction, University of Minnesota, Minneapolis, Minnesota
3Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota
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Jocelyn M. Richard
2Medical Discovery Team on Addiction, University of Minnesota, Minneapolis, Minnesota
3Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota
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    Figure 1.

    Characterization of DREADD localization and functional impact. A Representative section from the striatum (top), ventral pallidum (middle), and septum (bottom), used for analysis in QUINT workflow. B, Output results of QUINT workflow (n = 8), showing all brain regions where mCherry (DREADD virus reporter) was detected in rats that received 600 nl (n = 4, circles) and 800 nl (n = 4, triangles) injections. LME showed a significant effect of brain region (F(3,28) = 113.34, p < 0.001), on viral particles, with follow-up comparisons indicating that significantly more expression was found in VP compared with other brain regions where expression was seen. C, Percent of DREADD-positive cells expressing c-Fos after 0, 0.05, or 0.5 mg/kg J60 in male (circles) and female (triangles) rats expressing Gq or Gi DREADD. *p < 0.05 (left). D, Representative VP images from a Gq male (left) and a Gi male (right) injected with 0.5 mg/kg J60. E, Representative traces from neurons expressing mCherry (left) or Gi DREADD (right) during the baseline period and 0–5 and 5–10 min after J60 application. F, Normalized firing rate (% of baseline) of neurons expressing mCherry (black; 9 cells/3 rats) and Gi DREADD (red; 15 cells/3 rats) at baseline and following J60 wash-on (0–10 min). Lines and shading indicate mean ± SEM.

  • Figure 2.
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    Figure 2.

    Effects of chemogenetic activation of VP GABA neurons on sucrose consumption. A, A mixture of GAD1-cre and DIO-hM3Dq-mCherry or DIO-mCherry was injected bilaterally into the VP. B, Colormaps show hM3Dq viral placement (brightest point of expression) in a horizontal cross section of the VP and behavioral changes from baseline following a high dose (0.5 mg/kg) of J60, for all Gq (hM3Dq) rats (left), female Gq rats (middle), and male Gq rats (right). C, Sucrose consumption following injections of saline (light green), low-dose J60 (medium green), and high-dose J60 (dark green) for all Gq rats (left), Gq females (middle), and Gq males (right). D, Sucrose consumption following injections of saline (light green), low-dose J60 (medium green), and high-dose J60 (dark green) for all mCherry control rats (left), mCherry females (middle), and mCherry males (right). Bar plots and error bars indicate mean ± SEM. Dots and lines represent individual rats. Asterisks indicate p < 0.05 for Sidak-corrected pairwise comparisons.

  • Figure 3.
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    Figure 3.

    Effects of chemogenetic activation of VP GABA neurons on sucrose preference. A, Sucrose preference following injections of saline (light green), low-dose J60 (medium green), and high-dose J60 (dark green) for all Gq rats (left), Gq females (middle), and Gq males (right). B, Sucrose preference following injections of saline (light green), low-dose J60 (medium green), and high-dose J60 (dark green) for all mCherry control rats (left), mCherry females (middle), and mCherry males (right). Bar plots and error bars indicate mean ± SEM. Dots and lines represent individual rats. Asterisks indicate p < 0.05 for Sidak-corrected pairwise comparisons.

  • Figure 4.
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    Figure 4.

    Effects of chemogenetic activation of VP GABA neurons on chow consumption. A, Chow consumption following injections of saline (light green), low-dose J60 (medium green), and high-dose J60 (dark green) for all Gq rats (left), Gq females (middle), and Gq males (right). B, Chow consumption following injections of saline (light green), low-dose J60 (medium green), and high-dose J60 (dark green) for all mCherry control rats (left), mCherry females (middle), and mCherry males (right). Bar plots and error bars indicate mean ± SEM. Dots and lines represent individual rats. Asterisks indicate p < 0.05 for Sidak-corrected pairwise comparisons.

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Ventral Pallidal GABAergic Neurons Drive Consumption in Male, But Not Female, Rats
Alexandra Scott, Anika Paulson, Collin Prill, Klaiten Kermoade, Bailey Newell, Elizabeth A. Eckenwiler, Julia C. Lemos, Jocelyn M. Richard
eNeuro 14 January 2025, 12 (2) ENEURO.0245-24.2025; DOI: 10.1523/ENEURO.0245-24.2025

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Ventral Pallidal GABAergic Neurons Drive Consumption in Male, But Not Female, Rats
Alexandra Scott, Anika Paulson, Collin Prill, Klaiten Kermoade, Bailey Newell, Elizabeth A. Eckenwiler, Julia C. Lemos, Jocelyn M. Richard
eNeuro 14 January 2025, 12 (2) ENEURO.0245-24.2025; DOI: 10.1523/ENEURO.0245-24.2025
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Keywords

  • chemogenetic
  • consumption
  • sex differences
  • sucrose
  • ventral pallidum

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