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References

Introduction

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What is Anxiety? 

  • Anxiety disorder is an intensive, excessive, and persistent worry and fear about everyday situations
  • Affects 18% of the adult population each year or 40 million adults1

Why use rats as an animal models?

  • Genetic, biological, and behavioral characteristics closely resemble those of humans

Novelty of the current experiment

  • Subjects raised in a highly enriched environment, then reduced to a lower enriched environment in order to model the social impact of the COVID-19 pandemic

Behavioral tests for anxiety

  • Seconds spent in open arms of the elevated plus maze (EPM) positively correlated with anxiety like behavior in rats9

Brain structures targeted during neurochemical analysis

  • Amygdala takes in sensory information and associates it with an emotion2
  • Hypothalamus receives information from amygdala and sends out a fear response to the sympathetic nervous system3

Monoamines targeted during neurochemical analysis

  • Neurotransmitters involved in controlling the limbic system
  • Prior studies indicate norepinephrine (NE) and dopamine (DA) are positively correlated with anxiety in the Hypothalamus and Amygdala4,6
  • Serotonin (5-HT) negatively correlated with anxiety5

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Methods

Anxiety-like Behavioral and Monoamine Neurochemical Analysis of the Sudden Reduction

of Social Enrichment in Rats

Kylie Ramalhete, Nicole Spagna, Heather Wallace, Michael Welte, and Dr. Deborah Kreiss

First-year Research Immersion Program, Neuroscience stream, Binghamton University, Binghamton NY 13902

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Research Objective

To study the effects of paradoxical and total sleep deprivation on anxiety in rats 

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Discussion/Conclusions

Results

1. Adaa.org (2021) https://adaa.org/understanding-anxiety/facts-statistics. Accessed online 2021 November 1.

2. Rosen JB and Schulkin J (1998) From normal fear to pathological anxiety. Psychological Review. 105:325-350.

3. Rajmohan V and Mohandas E (2007) The limbic system. Indian Journal of Psychiatry. 49: 132-139.

4. Tanaka M, Yoshida M, Emoto H, and Ishii H (2000) Noradrenaline systems in the hypothalamus, amygdala and locus coeruleus are involved in the provocation of anxiety: basic studies. European Journal of Pharmacology. 405:397-406.

5. Berger M, Gray JA, Roth BL (2018) The expanded biology of serotonin. Annual Review of Medicine. 60:355-366.

6. Berke J (2018) What does dopamine mean? Nature Neuroscience. 21(6): 787-793.

7. Paxinos G and Watson C (1986) The Rat Brain in Stereotaxic Coordinates. Academic Press, NY.

8. Bishop C, George JA, Buchta W, Goldenberg AA, Mohamed M Dickinson, SO, Eissa S, and Eskow Jaunarajs KL (2012) Serotonin transporter inhibition attenuates l‐DOPA‐induced dyskinesia without compromising l‐DOPA efficacy in hemi‐parkinsonian rats. European Journal of Neuroscience. 36:2839-2848.

9. Walf AA and Frye CA (2007) The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nature Protocols. 2:322-328. 17:111-133.

10. Sturman O, Germain PL, and Bohacek J (2018) Exploratory rearing: A context and stress-sensitive behavior recorded in the open-field test. Stress. 21:443-452.

Research Objective

The overall goal was to evaluate the validity of this model to represent the isolating effects of the COVID-19 pandemic. The validity was assessed by analyzing the effects of sudden reduction of enrichment on anxiety-like behavior in rats using behavioral measurements (number of rears and time spent in the open arms of the EPM) and neurochemical analysis of monoamines present in the amygdala and hypothalamus of the post-mortem rats.

Behavioral Results

Acknowledgements

We would like to thank the entire FRI department, the BU laboratory animal resources staff, and Dr. Kreiss for giving us the opportunity to conduct this research. We would also like to thank all of our undergraduate course and lab TAs who have guided us through this process including Sarah Cerutti, Spencer Feehan, Amy Held, Christina Jacob, Hope Kellner, Rachel Lichtenstein, Alice Mazur, Chelsea McNamara, Hailey Robson, Andrei Smith, Shameeka Thompson, and Moss Tice. Thank you to cohort 8 of the FRI neuroscience stream. Thank you Sofia Figueroa and Laura Barlow for taking over 1,000 brain punches over summer 2022.

Neurochemical Results

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Seconds Spent in Open Arms

  • Time spent in the open arms was decreased in the control groups, but not in the experimental groups
  • Female experimental rats spent more time in the open arms than male experimental rats
  • ANOVA analysis showed a significant effect of enrichment (p = 0.004), trial (p = <0.001), and interactions between sex and enrichment (p = <0.001), sex and trial (p = 0.030), and enrichment and trial (p = 0.002)

Rears

  • Reduction of enrichment decreased the number of rears in male and female rats
  • Male experimental rats reared less than male control rats
  • ANOVA analysis showed a significant effect of enrichment (p = 0.021), trial (p = <0.001), and an interaction between sex and enrichment

(p = 0.054)

DA

  • ANOVA analysis of the amygdala data showed a significantt interaction between sex and enrichment (p = 0.038)

NE

  • ANOVA analysis of the amygdala data showed a significant interaction between sex and enrichment (p = 0.034)
  • ANOVA analysis of the hypothalamus data showed a significant effect of enrichment (p = 0.050), sex (p = 0.018), and an interaction between sex and enrichment (p = 0.019)

5-HT

  • ANOVA analysis of the hypothalamus data showed a significant effect of sex (p = <0.001)
  • ANOVA analysis of the amygdala data showed a trend toward a significant effect of sex (p=0.080)

Behavioral Correlations

  • In both trials, rears and seconds in the open arms correlated for the male control group only
  • Studies show number of rears is negatively correlated with anxiety-like behavior in rats10

Additional Neurochemical Results

  • Experimental females had lower levels of NE in the hypothalamus than male counterparts
  • In males, reduction of enrichment increased NE in the hypothalamus
  • In females, reduction of enrichment decreased NE in the hypothalamus and decreased DA in the amygdala
  • Control females had higher levels of NE and DA and less 5-HT in the amygdala as compared to control males
  • Female groups had higher levels of 5-HT in the hypothalamus as compared to corresponding male groups
  • Reduction of enrichment decreased the number of rears in female and males
  • Sex influences time spent in the open arms