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Research ArticleResearch Article: New Research, Disorders of the Nervous System

Nicotine Self-Administration Induces Plastic Changes to Nicotinic Receptors in Medial Habenula

Xiao-Tao Jin, Brenton R. Tucker and Ryan M. Drenan
eNeuro 16 July 2020, 7 (4) ENEURO.0197-20.2020; https://doi.org/10.1523/ENEURO.0197-20.2020
Xiao-Tao Jin
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC 27157
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Brenton R. Tucker
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC 27157
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Ryan M. Drenan
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC 27157
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    Figure 1.

    Nicotine SA representative results. A, Nicotine SA training history for rat #167002 is shown as a raster plot. Each nose poke response (active resulting in an infusion: red; inactive: black) during the 2-h SA session is represented as a vertical tick mark. SA sessions, from first to 15th, are plotted from bottom to top; *denotes sessions plotted in further detail in B, C. B, C, Cumulative response plot for session #1 (B) and #10 (C) are shown for nicotine SA rat #167002. Active nose pokes that occurred during the timeout period, which did not result in a nicotine infusion, are shown as upward-going blue tick marks. D, Saline SA training history for rat #163464 is shown as a raster plot. Each nose poke response (active resulting in an infusion: red; inactive: black) during the 2-h SA session is represented as a vertical tick mark. SA sessions, from first to 15th, are plotted from bottom to top; *denotes sessions plotted in further detail in E, F. E, F, Cumulative response plot for session #1 (E) and #10 (F) are shown for nicotine SA rat #163464. Active nose pokes that occurred during the timeout period, which did not result in a saline infusion, are shown as upward-going blue tick marks.

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    Figure 2.

    Nicotine SA summary results. A, Nicotine SA responses. Mean (±SEM) active and inactive nose pokes for n = 15 male rats are shown for sessions #1–15 of nicotine SA. B, Saline SA responses. Mean (±SEM) active and inactive nose pokes for n = 12 male rats are shown for sessions #1–15 of saline SA. C, Gardner–Altman plot of active nose poke responses on SA session #10 for nicotine SA and saline SA groups. The effect size (mean difference) and bootstrap 95% CI are shown at right. D, Nicotine versus saline infusions. Mean (±SEM) # of nicotine and saline infusions earned are shown for SA sessions #1–15. E, Gardner–Altman plot of infusions earned on SA session #10 for nicotine SA and saline SA groups. The effect size (mean difference) and bootstrap 95% CI are shown at right. F, Nicotine intake. Mean (±SEM) nicotine intake is shown for the nicotine SA group for SA sessions #1–15.

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    Figure 3.

    nAChR functional upregulation in MHb. A, Experiment schematic. Coronal brain slices containing MHb were prepared from rats after the last SA session. MHb neurons were patch clamped and ACh was locally applied to the neuron to evoke nAChR currents. B, nAChR representative responses in nicotine SA versus yoked saline rats. Responses from the same MHb neuron to the indicated ACh pulse duration are shown for nicotine SA or yoked saline control. C, Summary concentration response data for nicotine SA versus yoked saline. Mean (±SEM) ACh-evoked current amplitude is shown for the indicated ACh pulse duration for recordings from MHb neurons from nicotine SA and yoked saline control rats. D, Heat map representation of ACh-evoked currents. For 100-ms ACh pulses in the nicotine SA and yoked saline control groups, individual cellular responses comprising the second and third quartiles are expressed as a heat map scaled to the response with the greatest magnitude (a nicotine SA response). E, Summary concentration response data for nicotine SA versus saline SA. Mean (±SEM) ACh-evoked current amplitude is shown for the indicated ACh pulse duration for recordings from MHb neurons from nicotine SA and saline SA rats. Nicotine SA data from C are re-plotted for comparison to the saline SA control group. F, Heat map representation of ACh-evoked currents. For 100-ms ACh pulses in the nicotine SA and saline SA groups, individual cellular responses comprising the second and third quartiles are expressed as a heat map scaled to the response with the greatest magnitude (a nicotine SA response). G, Gardner–Altman plot of peak ACh-evoked current (100-ms pulse duration) for nicotine SA versus yoked saline control. The effect size (median difference) and bootstrap 95% CI are shown at right. H, Gardner–Altman plot of peak ACh-evoked current (100-ms pulse duration) for nicotine SA versus saline SA. The effect size (median difference) and bootstrap 95% CI are shown at right.

  • Figure 4.
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    Figure 4.

    Nicotine SA boosts nAChR function at the soma and in dendrites. A, Experiment schematic. Coronal brain slices containing MHb were prepared from rats after the last SA session. MHb neurons were patch clamped, neuronal morphology was imaged with 2PLSM, and nicotine was uncaged via laser flash photolysis. B, Representative nicotine uncaging experiment. An exemplar two-photon image of a MHb neuron is shown, along with locations (soma, proximal dendrite, distal dendrite) where nicotine was uncaged and the recorded nAChR response to such uncaging. C, Proximal dendrite uncaging responses. Heat map representations of proximal dendrite nicotine uncaging responses from individual neurons are shown for nicotine SA and saline SA rats. All heat maps are scaled to the response with the greatest magnitude (a nicotine SA response). D–F, Gardner–Altman plots of peak nicotine uncaging currents at the soma (D), proximal dendrite (E), and distal dendrite (F). At left, scatter plots show individual uncaging currents for nicotine SA and saline SA rats. At right, the effect size (median difference) and bootstrap 95% CI are shown.

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Nicotine Self-Administration Induces Plastic Changes to Nicotinic Receptors in Medial Habenula
Xiao-Tao Jin, Brenton R. Tucker, Ryan M. Drenan
eNeuro 16 July 2020, 7 (4) ENEURO.0197-20.2020; DOI: 10.1523/ENEURO.0197-20.2020

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Nicotine Self-Administration Induces Plastic Changes to Nicotinic Receptors in Medial Habenula
Xiao-Tao Jin, Brenton R. Tucker, Ryan M. Drenan
eNeuro 16 July 2020, 7 (4) ENEURO.0197-20.2020; DOI: 10.1523/ENEURO.0197-20.2020
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Keywords

  • Acetylcholine
  • addiction
  • habenula
  • nicotine
  • relapse
  • tobacco

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