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Featured ArticleArticles, Behavioral/Systems/Cognitive

Uncontrollable, But Not Controllable, Stress Desensitizes 5-HT1A Receptors in the Dorsal Raphe Nucleus

Robert R. Rozeske, Andrew K. Evans, Matthew G. Frank, Linda R. Watkins, Christopher A. Lowry and Steven F. Maier
Journal of Neuroscience 5 October 2011, 31 (40) 14107-14115; DOI: https://doi.org/10.1523/JNEUROSCI.3095-11.2011
Robert R. Rozeske
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Andrew K. Evans
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Matthew G. Frank
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Linda R. Watkins
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Christopher A. Lowry
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Steven F. Maier
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    Figure 1.

    A, Placements of microinjection cannulae in the mPFC. Black circles indicate the location of the cannulae tips. B, Location of single-unit extracellular recordings in the DRN. The gray-shaded areas indicate where recordings were preferentially taken. Numerals indicate distance from bregma in millimeters. Anatomical maps adopted from Paxinos and Watson (1998).

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    Figure 2.

    Spike frequency histograms from extracellular single-unit recordings in the DRN after HC control (A), ES (B), and IS (C). Midbrain slices were taken 24 h after stress treatment, and varying doses of 5-HT were applied. Mean percentage inhibition was calculated to account for the rate at which the cell reaches maximal serotonin-mediated inhibition.

  • Figure 3.
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    Figure 3.

    IS selectively impairs serotonin-mediated inhibition of DRN cell firing 24 h after stress treatment. The graph depicts the effect of stress treatment on serotonin-mediated inhibition of DRN cell firing. Groups are designated as the following: HC, filled triangles; ES, filled squares; IS, open circles. Data are expressed as mean ± SEM percentage inhibition. Mean percentage inhibition of DRN cell firing was significantly different in IS compared to ES and HC (p < 0.05).

  • Figure 4.
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    Figure 4.

    IS impairs ipsapirone-mediated inhibition of dorsal raphe nucleus cell firing 24 h after stress treatment. Groups are expressed as the following: HC, filled squares; IS, open circles. Data are expressed as mean ± SEM percentage inhibition. IS significantly reduced mean percentage inhibition of ipsapirone-mediated inhibition of DRN cell firing compared with HC (p < 0.001). *p < 0.05, mean ipsapirone-mediated inhibition was significantly different between IS and HC at the 150 and 250 nm doses.

  • Figure 5.
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    Figure 5.

    Ipsapirone-mediated inhibition of DRN 5-HT cell firing is selectively impaired 24 h after IS. The white bar indicates non-stressed HC, the gray bar indicates IS rats that were killed immediately after IS, the black bar indicates rats killed 24 h after IS, and the patterned bar represents rats that were killed 7 d after IS. The data are expressed as mean + SEM percentage inhibition. Mean percentage inhibition was significantly different among groups (p < 0.05). *p < 0.05, Dunnett's multiple comparison test revealed that only the 24 h time point was significantly different from HC.

  • Figure 6.
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    Figure 6.

    Spike frequency histograms from extracellular single-unit recording in the dorsal raphe nucleus after intra-mPFC injection of muscimol during HC (A), intra-mPFC muscimol during IS (B), intra-mPFC muscimol during ES (C), and intra-mPFC saline during ES (D). Midbrain slices were taken 24 h after stress treatment, and 50 μm 5-HT was applied, followed by 150 nm ipsapirone. Mean percentage inhibition was calculated to account for the rate at which the cell reaches maximal ipsapirone-mediated inhibition.

  • Figure 7.
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    Figure 7.

    A microinjection of muscimol into the mPFC during ES impairs inhibition of DRN 5-HT cell firing with 150 nm ipsapirone. Open bars indicate rats that received intra-mPFC saline, and filled bars indicate rats that received intra-mPFC muscimol microinjections. Data are expressed as mean + SEM percentage inhibition. Mean percentage inhibition of DRN 5-HT cell firing was significantly different between IS and HC treatments (p < 0.05). *p < 0.05, mean percentage inhibition of DRN 5-HT cell firing was significantly different between ES rats receiving intra-mPFC muscimol and saline.

  • Figure 8.
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    Figure 8.

    Spike frequency histograms from extracellular single-unit recording in the DRN 24 h after home-cage control (HC/HC) (A), home-cage control followed 24 h later by inescapable stress (HC/IS) (B), and escapable stress followed 24 h later by inescapable stress (ES/IS) (C). Midbrain slices were taken 24 h after final stress treatment, and 50 μm 5-HT was applied, followed by 150 nm ipsapirone. Mean percentage inhibition was calculated to account for the rate at which the cell reaches maximal ipsapirone-mediated inhibition.

  • Figure 9.
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    Figure 9.

    Behavioral immunization blocks IS-induced impairment of DRN 5-HT cell firing with 150 nm ipsapirone. Data are expressed as mean ± SEM percentage inhibition. Mean percentage inhibition was different among stress groups (p < 0.05). *p < 0.05, mean percentage inhibition of DRN 5-HT cell firing was significantly different in rats that received home-cage treatment followed by IS (HC/IS) compared with rats that received no stress (HC/HC) and behavioral immunization (ES/IS).

  • Figure 10.
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    Figure 10.

    Protein expression of 5-HT1A-R in the DRN is not changed 24 h after IS and HC treatments. Representative Western blot of 5-HT1A-R and Na-K ATPase expression in the DRN 24 h after IS and HC treatments. No significant difference was observed between HC and IS treatments (p > 0.05).

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The Journal of Neuroscience: 31 (40)
Journal of Neuroscience
Vol. 31, Issue 40
5 Oct 2011
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Uncontrollable, But Not Controllable, Stress Desensitizes 5-HT1A Receptors in the Dorsal Raphe Nucleus
Robert R. Rozeske, Andrew K. Evans, Matthew G. Frank, Linda R. Watkins, Christopher A. Lowry, Steven F. Maier
Journal of Neuroscience 5 October 2011, 31 (40) 14107-14115; DOI: 10.1523/JNEUROSCI.3095-11.2011

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Uncontrollable, But Not Controllable, Stress Desensitizes 5-HT1A Receptors in the Dorsal Raphe Nucleus
Robert R. Rozeske, Andrew K. Evans, Matthew G. Frank, Linda R. Watkins, Christopher A. Lowry, Steven F. Maier
Journal of Neuroscience 5 October 2011, 31 (40) 14107-14115; DOI: 10.1523/JNEUROSCI.3095-11.2011
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