Transcript www.drew.edu

Three Tails of Twelve Anxious
Rats: Effects of Stressors on
Animal Models of Anxiety
Team 4:
Daniel Cho, Robyn Guo, Siddharth Hariharan,
George Jiang, Nicole Jisoo Kim, Julia Nicholas,
Yesha Parekh, Christina Qiu, Sohum Shah,
Priyanka Singh, Pearl Subramanian, Amanda Weiss
Anxiety/Anxiety Disorders?
● What is anxiety?
● What is an anxiety disorder?
● Various forms of Anxiety Disorders
o Panic attacks, Social Anxiety, Phobias
● Most common mental illness in the US
o Public health
Anxiety v. Anxiety Disorder
Regular Anxiety
Anxiety Disorder
Being nervous about applying to
Governor’s School
Having random panic attacks and
losing your appetite because of team
projects
Having trouble sleeping after an
immediate traumatic event
Having flashbacks or recurring
nightmares about a traumatic event
that occurred months or years before
Acoustic Startle Response
http://www.animalab.pl/wp-content/uploads/2013/05/Startle-responsesystem1.jpg
Three Tails
1. Parametric Testing: Does our
equipment work?
a. Acoustic Startle Response (ASR)
b. Prepulse Inhibition (PPI)
2. What does stress do to anxiety?
a. Light Enhanced Startle (LES)
b. Zero Maze
3. What does stress do to phasic fear?
a. Fear Potentiated Startle (FPS)
Tail 1: Parametric Tests
ASR increases with pulse intensity and habituates across sessions
Prepulse Inhibition (PPI) Shows That a
Prepulse Lowers Startle Response
No PrePulse
PrePulses
Tail 2: What does stress do to
anxiety?
Restraint Stress
Immediate PostTest
Baseline Test:
Restraint Stress
(1 hour) (n=6)
2 days
Delayed Post-Test
Control Treatment (n=5)
Light-Enhanced Startle (LES)
Block 1
http://homepage.psy.utexas.edu/homepage/class/Psy308/Salinas/Emotion/Startle.gif
Block 2
Block 3
LES is not significantly different between
groups of rats in Pre-Test
Baseline (Dark)
Light
Dark
LES at 90 dB in a pre-test, immediate post-test,
and delayed post-test
Comparison of blocks 2+3 to block 1 (90 dB)
Zero Maze Track Plots
Control
Restraint
Restraint Stress Mildly Increases Time in
Open Arms During Delayed Post-Test
No Correlation Between Zero Maze & LES
Tail 3: What does stress do to phasic
fear?
Phasic and Sustained Fear
Stressor
Phasic
Sustained
FPS was Predicted to Accentuate the Startle
in the Presence of the Conditioned Stimulus
Conclusion
Tail 1: Equipment works; correlation between greater
intensity of pulse and startle response and PPI
Tail 2: LES present, but cannot determine relationship
to stress; Zero Maze-there might be an effect of the
stressor but further testing is required; no correlation
between LES and zero maze
Tail 3: No evidence of FPS; no conclusion of stress on
phasic fear
Future Experimentation
Number of Rats
Zero Maze
Modified Stress
Construction
Handling
measuring CRH release
Changes in Structure & Function of Amygdala
References
1. Anxiety and physical illness. 2008 Jul. Harvard Health Publications; Available from
<http://www.health.harvard.edu/newsletters/Harvard_Womens_Health_Watch/2008/July/Anxiety_and_physical_illness>
2. Yoon SH, Kim BH, Ye SK, Kim MH. Chronic non-social stress affects depressive behaviors but not anxiety in mice. Korean J Physiol
Pharmacol. Jun 2014; 18(3):263-268.
3. aan het Rot M, Mathew SJ, Charney DS. Neurobiological mechanisms in major depressive disorder. CMAJ. 2009;180:305–313.)
4. Pittenger C, Duman RS. Stress, depression, and neuroplasticity: a convergence of mechanisms. Neuropsychopharmacology.2008;33:88–109.
5. Davis, D. Walker, D. Miles, L. and Grillon, C. Neuropsychopharmacology (2010) 35, 105–135; doi:10.1038/npp.2009.109; published online
19 August 2009.
6. Koch M. The Neurobiology of Startle. Prog Neurobiol. 1999 Oct;59(2):107-28.
7. Valsamis, B., Schmid, S. Habituation and Prepulse Inhibition of Acoustic Startle in Rodents. J. Vis. Exp. (55), e3446, doi:10.3791/3446
(2011).
8. Merali Z, Khan S, Michaud DS, Shippy SA, Anisman H. Does amygdaloid corticotropin-releasing hormone (CRH) mediate anxiety-like
behaviors? Dissociation of anxiogenic effects and CRH release. Eur J Neurosci. 2004 Jul;20(1):229-39.
9. Med Associates SOF-826 Startle-PPI Program Manual
10.Zhang W, Hetzel A, Shah B, Atchley D, Blume SR, Padival MA, Rosenkranz JA. Greater physiological and behavioral effects of interrupted
stress pattern compared to daily restraint stress in rats. PLoS One. 2014; 9(7): e102247.
11. Merlo PE, Lorang M, Peganeh M, Rodriguez de Foseca F, Raber J, Koob GF, Weiss F. Increase of extracellular corticotropin-releasing
factor-like immunoreactivity level in the amygdala of awake rats during restraint stress and ethanol withdrawal as measured by microdialysis. J
Neurosci. 1995 Aug; 15(8):5439-47.
12. Martin GF, Holstege G, Mehler WR. Reticular formation of the pons and medulla. Ed G Paxinos Ac Pres. 1990; 203-220.
Acknowledgements
● Dr Graham Cousens
● Sana Siddiqui
● Our rats: Simon the Scrub, Bob, Miley, Blue Ivy, Luis Suarez, Kim, Ne-Yo, Drake,
Chris Brown, Jay-Z, Beyonce, and Kanye.
● Funders and Supporters of NJGSS:
o
o
o
o
o
o
o
o
o
o
o
Independent College Fund of NJ/ Johnson & Johnson
AT&T
Actavis Pharmaceuticals
Bayer Healthcare
Celgene
Novartis
Laura (NJGSS ‘86) and John Overdeck
NJGSS Alumnae and Parents of Alumnae
Board of Overseers, New Jersey’s Governor’s Schools
State of New Jersey
Drew University