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Research ArticleResearch Article: New Research, Integrative Systems

Ventral Tegmental Area Amylin Receptor Activation Differentially Modulates Mesolimbic Dopamine Signaling in Response to Fat versus Sugar

Rohan V. Bhimani, Lily Rzepecki, Jinwoo Park and Elizabeth G. Mietlicki-Baase
eNeuro 28 May 2024, 11 (6) ENEURO.0133-24.2024; https://doi.org/10.1523/ENEURO.0133-24.2024
Rohan V. Bhimani
1Neuroscience Program, University at Buffalo, State University of New York, Buffalo, New York 14214-3005
2Department of Biotechnical and Clinical Laboratory Sciences, University at Buffalo, State University of New York, Buffalo, New York 14214-3005
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Lily Rzepecki
2Department of Biotechnical and Clinical Laboratory Sciences, University at Buffalo, State University of New York, Buffalo, New York 14214-3005
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Jinwoo Park
1Neuroscience Program, University at Buffalo, State University of New York, Buffalo, New York 14214-3005
2Department of Biotechnical and Clinical Laboratory Sciences, University at Buffalo, State University of New York, Buffalo, New York 14214-3005
3Department of Pharmacology and Toxicology, University at Buffalo, State University of New York, Buffalo, New York 14214-3005
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Elizabeth G. Mietlicki-Baase
1Neuroscience Program, University at Buffalo, State University of New York, Buffalo, New York 14214-3005
4Department of Exercise and Nutrition Sciences, University at Buffalo, State University of New York, Buffalo, New York 14214-3005
5Center for Ingestive Behavior Research, University at Buffalo, State University of New York, Buffalo, New York 14214-3005
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  • Figure 1.
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    Figure 1.

    Effects of VTA amylin receptor activation on modulating sucrose-enhanced DA in the NAcC. Average color plots (top) show background subtracted cyclic voltammograms collected 5 s before and 14 s after administration of sucrose from a single rat. DA concentration changes were seen in the color plot at the potential (Eapp) for DA oxidation (∼0.65 V, dotted white line) in response to intraoral sucrose administration before and after aCSF (A) or sCT (B) administration following principal component analysis. A representative average cyclic voltammogram is highlighted in Figure 1B from a point in the concentration versus time trace (indicated by blue arrow). Red line and red bar on the DA concentration trace indicates standard error and duration of sucrose infusion (4 s), respectively. C, Trial by trial maximal DA responses ([DA]max) before [termed “Sucrose (Pre-drug)”] and after vehicle (aCSF, blue line) or amylin receptor agonist (sCT, orange line) administration. D, sCT significantly decreased average maximal DA concentration in response to sucrose compared with vehicle (aCSF) administration. E, Electrode recording sites in the NAcC for animals used in sucrose experiments (top) and representative electrolytical lesion (bottom). F, sCT and aCSF injection sites for animals used in sucrose experiments (top) and representative dye infusion in the VTA (bottom) indicating where drug was injected. ***p < 0.001.

  • Figure 2.
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    Figure 2.

    Effects of VTA amylin receptor activation on modulating Intralipid-enhanced DA in the NAcC. Average color plots (top) show background subtracted cyclic voltammograms collected 5 s before and 14 s after administration of Intralipid from a single rat. DA concentration changes were seen in the color plot at the potential (Eapp) for DA oxidation (∼0.65 V, dotted white line) in response to intraoral Intralipid administration before [termed “Intralipid (Pre-drug)”] and after aCSF (A) or sCT (B) administration following principal component analysis. The inset shows the concentration versus time trace following sCT administration at a higher magnification. Red line and red bar on the DA concentration trace indicates standard error and duration of Intralipid infusion (4 s), respectively. C, Trial by trial maximal DA responses before and after vehicle (aCSF, blue line) or amylin receptor agonist (sCT, orange line) administration. D, sCT significantly decreased average maximal DA concentration in response to sucrose compared with vehicle (aCSF) administration. E, Electrode recording sites for animals used in sucrose experiments (top) and representative electrolytical lesion (bottom). F, sCT and aCSF injection sites for animals used in sucrose experiments (top) and representative dye infusion in the VTA (bottom) indicating where drug was injected. ****p < 0.0001.

  • Figure 3.
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    Figure 3.

    Comparison of sucrose (Suc) and Intralipid (IL) effects on NAcC DA. A, Average DA concentration versus time traces across all animals for sucrose (blue) and Intralipid (red) administration. The dotted lines indicate standard error from mean (solid line). B, Average maximal DA concentration (nM) changes in response to intraoral sucrose or Intralipid administration before sCT or vehicle (aCSF) injection. *p < 0.05.

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    Figure 4.

    Effects of the amylin receptor agonist (sCT) on naturally occurring phasic dopamine transmission. A, B, Representative color plots show background subtracted cyclic voltammograms collected before (left) and 30 min after (right) administration of aCSF (top) or sCT (bottom) from single rats. DA concentration changes were seen in the color plot at the potential (Eapp) for DA oxidation (∼0.65 V, dotted white line). Red reversed triangles indicate phasic dopamine transients. A representative cyclic voltammogram from a phasic dopamine transient is highlighted in Figure 4A from a point in the concentration versus time trace (indicated by blue arrow).

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    Table 1.

    Average maximal DA concentration changes ([DA]max, nM) following intraoral administration of sucrose or Intralipid after VTA injection of either aCSF or sCT

    Drug[DA]max to sucrose (n = 6 rats/condition)[DA]max to intralipid (n = 6 rats/condition)
    aCSF59.7 ± 8.1 nM88.8 ± 10.5 nM
    sCT33.8 ± 3.2 nM15.8 ± 3.1 nM
    • Data are presented as means ± SEM.

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    Table 2.

    Average naturally occurring phasic dopamine transient concentration (nM) and frequency (Hz) before and after VTA injection of either aCSF or sCT

    DrugDopamine concentration (nM)Frequency (Hz)
    Predrug43.9 ± 2.50.38 ± 0.03
    aCSF45.4 ± 0.2.70.37 ± 0.03
    sCT43.8 ± 2.40.37 ± 0.02
    • Data are presented as means ± SEM.

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June 2024
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Ventral Tegmental Area Amylin Receptor Activation Differentially Modulates Mesolimbic Dopamine Signaling in Response to Fat versus Sugar
Rohan V. Bhimani, Lily Rzepecki, Jinwoo Park, Elizabeth G. Mietlicki-Baase
eNeuro 28 May 2024, 11 (6) ENEURO.0133-24.2024; DOI: 10.1523/ENEURO.0133-24.2024

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Ventral Tegmental Area Amylin Receptor Activation Differentially Modulates Mesolimbic Dopamine Signaling in Response to Fat versus Sugar
Rohan V. Bhimani, Lily Rzepecki, Jinwoo Park, Elizabeth G. Mietlicki-Baase
eNeuro 28 May 2024, 11 (6) ENEURO.0133-24.2024; DOI: 10.1523/ENEURO.0133-24.2024
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Keywords

  • macronutrient
  • nucleus accumbens
  • palatable food
  • reward
  • voltammetry
  • VTA

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