Presentation#407.7 /Poster #NNN5
Animal model of post-traumatic stress disorder (PTSD): Effects of propranolol on exploration in an elevated plus maze in rats
G.H. Gotthard, J. Marini, S. Mangel, J. Block, D. Tate, C. Hackmyer, and C. Burgdorf
Muhlenberg College
Allentown, PA 18104
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Introduction
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Test 2
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PTSD is an anxiety disorder that is caused by exposure to a traumatic, often lifethreatening, event. One relatively new line of research is employing β-blockers (drugs that
lower adrenaline) to weaken traumatic memories. In a limited number of studies, βblockers were given to human participants shortly after a traumatic event to prevent PTSD
from forming (Pitman et al., 2001; Vaiva et al., 2003). In these studies, when β-blockers
were given shortly after trauma, the development of PTSD was significantly less than with
a placebo.
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While preliminary research into the use of β-blockers for PTSD prevention is encouraging,
there is still a considerable amount of work that needs to be done before these treatments
can be safely used with PTSD patients. And because many of the manipulations that need
to be carried out cannot ethically be done with human participants, an animal model of
PTSD would be a valuable tool.
A limited number of animal models of PTSD exist in the literature, and none use a full
sensory experience (Cohen et al., 2006; Do Monte et al., 2008). Both use predator threat
as the traumatic event, but with limited sensory modalities. The proposed study aimed to
more carefully quantify the feared stimulus as a full sensory experience, so that it could be
consistent from one exposure to the next. In the present study, rats were exposed to a dog
followed by a test for anxiety reactions on an elevated plus maze. After the plus maze test,
rats received an injection of propranolol (β-blocker) or vehicle (distilled water). One week
later, rats were tested again on the elevated plus maze to examine long-term effects of
predator exposure and to examine the effects of propranolol on attenuating that anxiety
reaction. One month after predator exposure, rats were trained on the sand maze (an
appetitive spatial task) to examine the long-term fear-attenuating effects of propranolol.
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Discussion
• The animal model of PTSD presented in this study served as an effective means to
produce a fear reaction in rats (as evidenced by less exploration on an EPM test
following exposure).
• Propranolol presented after predator exposure effectively attenuated fear, which resulted
in increased levels of exploration on an EPM test one week following exposure.
• The same fear attenuating effects seen on the EPM test did not carry over to later
learning in an appetitive spatial task. This can be seen by shorter latencies to find the
buried reward by non-exposed rats, as compared to exposed rats (both propranolol and
vehicle).
• Future studies in our lab will further refine this animal model of PTSD. For example,
critical control groups, like non-exposed propranolol-injected or vehicle-injected rats,
need to be included in future studies using this model to rule out effects of injection
and/or propranolol on behavior in general.
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Exp: Propranolol
Exp: Vehicle
Non-Exposed
Figure 2. Plus Maze Exploration: Exposure to a predator resulted in increased fear (as
evidenced by decreased exploration in the elevated plus maze, EPM) that was alleviated
by post-exposure injections of propranolol .
Post-Exposure EPM Test (Test 1): A one-way ANOVA revealed statistically significant
differences in exploration between groups [F(2,17)=21.712, p<.0001]. Tukey post hoc
analyses indicated that rats exposed to the predator explored less than non-exposed
control rats (p<.0001), with no differences between exposed rats that would later receive
propranolol or vehicle (p>.05).
One-Week EPM Test (Test 2): A one-way ANOVA revealed statistically significant
differences in exploration between groups [F(2,17)=8.291, p<.01]. Tukey post hoc
analyses showed that exposed propranolol rats explored significantly more than exposed
vehicle rats (p<.01), and did not differ significantly from non-exposed control rats
(p>.05).
Method
Apparatus
Predator and room exposures were carried out in a Plexiglas cage identical to the rats’
home cages (that was thoroughly cleaned following each rat’s trial). An elevated plus
maze (EPM) (Harvard Apparatus) was used to collect dependent measures of exploration.
A sand maze apparatus (Gotthard, 2006) was used to collect dependent measures of ability
to learn a spatial task.
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Latency to Obtain Reward (in seconds)
Subjects
Ninety-day old, naïve, male Long-Evans rats (N=20) were used in the present study. Water
and food was available ad libitum. Animals were kept on a 12 hour light/dark cycle, with
the lights coming on at 7:00 a.m. All procedures employed in the present study were
approved by the IACUC at Muhlenberg College prior to experimentation.
References
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Exposed: Propanolol
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Exposed: Vehicle
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Unexposed Control
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Day
Figure 3. Sand Maze Acquisition: The fear attenuating effects of propranolol did not
transfer to learning a new task one month after predator exposure. A one-way ANOVA
revealed statistically significant differences in latency for location acquisition in the sand
maze [Day 1: F(2, 21)=6.325 , p< .01; Day 2: F(2, 21)=9.373 , p< .001; Day 3:
F(2,21)=14.477 , p< .001; Day 4: F(2, 21)=16.491 , p< .001]. LSD post hoc analyses
showed that propranolol rats did not differ significantly from vehicle rats on latency to
find the reward (p>.05), while unexposed controls differed significantly from propranolol
and vehicle groups (p< 0.01).
Figure 1. Procedure of exposure, drug injections, and testing
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Acknowledgments
•Dr. Jeremy Teissere
•Muhlenberg College Dean’s Office
•Dana Associates
•Sentience Foundation
•R.J. Fellows