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Research ArticleResearch Article: New Research, Sensory and Motor Systems

A Vestibular Challenge Combined with Calcitonin Gene-Related Peptide (CGRP) Promotes Anxiety-Like Behaviors

Shafaqat M. Rahman, Catherine Hauser, Stefanie Faucher, Elana Fine and Anne E. Luebke
eNeuro 12 July 2024, 11 (7) ENEURO.0270-23.2024; https://doi.org/10.1523/ENEURO.0270-23.2024
Shafaqat M. Rahman
1Department of Biomedical Engineering, University of Rochester, Rochester, New York 14627
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Catherine Hauser
1Department of Biomedical Engineering, University of Rochester, Rochester, New York 14627
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Stefanie Faucher
1Department of Biomedical Engineering, University of Rochester, Rochester, New York 14627
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Elana Fine
1Department of Biomedical Engineering, University of Rochester, Rochester, New York 14627
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Anne E. Luebke
1Department of Biomedical Engineering, University of Rochester, Rochester, New York 14627
2Department of Neuroscience, Del Monte Institute of Neuroscience, University of Rochester Medical Center, Rochester, New York 14642
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    Figure 1.

    CGRP and OVAR on EPM behaviors. A, The EPM and its components are shown on the left, an experimental timeline is provided on the right, and an equation for calculating the anxiety index is provided underneath. B, C, In 33 mice (17M/16F), two-way RM ANOVAs with Tukey’s post hoc analyses were used to evaluate B, anxiety indices, and C, center bouts due to either i.p. vehicle or i.p. CGRP as well as these i.p. injections to a brief (30 s) OVAR. Symbols are depicted: female (F), orange circle; male (M), blue square. B, Only OVAR after CGRP injection significantly increased anxiety indices in all mice. C, OVAR-induced anxiety strongly affected the number of center bouts detected in both females and males during both vehicle and CGRP testing. P-values and asterisks are listed: *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001.

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    Figure 2.

    CGRP and OVAR on rotarod configured with two different dowels. A, Rotarod configured with a mouse or rat dowel is shown, and an experimental timeline highlighting training and experiment days is provided. Twenty mice (10M/10F) were tested with the mouse dowel, and 39 mice (20M/19F) were tested with the rat dowel. Two-way RM ANOVAs with Tukey’s multiple-comparisons test was used to evaluate maximum LTF. B–D, A disrupted pre-VC rotarod ability due to CGRP is observed in males (Fig. 2C). Again, after OVAR, there was a significant difference in males between i.p. vehicle and i.p. CGRP. E–G, Contrary to mouse dowel studies, rat dowel studies indicated an effect of OVAR but not systemic CGRP. OVAR reduced rotarod ability in female mice treated with i.p. vehicle Again, in female mice specifically, maximum LTFs dropped from vehicle to vehicle/post-OVAR, but this was not seen in males. P-values and asterisks are listed: *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001.

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    Table 1.

    Anxiety index and bouts through the center were computed using three-way mixed-effects models, while rotarod data using the mouse dowel (r = 1.5 cm) and rat dowel (r = 3.5 cm) was computed using three-way ANOVAs

    Behavioral outcomeFactorsF (DFn, DFd)p-value
    Anxiety indexVehicle versus CGRPF(1.00, 31.00) = 1.55n.s.
    Pre- versus post-OVARF(1.00, 31.00) = 58.50p < 0.0001
    Male versus femaleF(1.00, 14.00) = 0.80n.s.
    Bouts through centerVehicle versus CGRPF(1.00, 31.00) = 0.47n.s.
    Pre- versus post-OVARF(1.00, 31.00) = 188.00p < 0.0001
    Male versus femaleF(1.00, 14.00) = 3.74n.s.
    Rotarod—mouse dowelVehicle versus CGRPF(1.00, 18.00) = 29.07p < 0.0001
    Pre- versus post-OVARF(1.00, 18.00) = 0.07n.s.
    Male versus femaleF(1.00, 18.00) = 0.17n.s.
    Rotarod—rat dowelVehicle versus CGRPF(1.00, 37.00) = 0.17n.s.
    Pre- versus post-OVARF(1.00, 37.00) = 21.03p < 0.0001
    Male versus femaleF(1.00, 37.00) = 1.88n.s.
    • For all multivariate analyses, we examined the following three factors: treatment (i.p. vehicle vs i.p. CGRP), VC (pre- vs post-OVAR), and biological sex (male vs female). F-values are listed with respect to degrees of freedom (DFn, DFd) and p-values are listed accordingly.

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A Vestibular Challenge Combined with Calcitonin Gene-Related Peptide (CGRP) Promotes Anxiety-Like Behaviors
Shafaqat M. Rahman, Catherine Hauser, Stefanie Faucher, Elana Fine, Anne E. Luebke
eNeuro 12 July 2024, 11 (7) ENEURO.0270-23.2024; DOI: 10.1523/ENEURO.0270-23.2024

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A Vestibular Challenge Combined with Calcitonin Gene-Related Peptide (CGRP) Promotes Anxiety-Like Behaviors
Shafaqat M. Rahman, Catherine Hauser, Stefanie Faucher, Elana Fine, Anne E. Luebke
eNeuro 12 July 2024, 11 (7) ENEURO.0270-23.2024; DOI: 10.1523/ENEURO.0270-23.2024
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Keywords

  • anxiety
  • calcitonin gene-related peptide (CGRP)
  • mouse models
  • rotarod and elevated plus maze
  • vestibular
  • vestibular migraine

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