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J A M I L A P I T T S , J E F F R E Y H S U , T E R E S A M A D S E N ,
P H . D , A D V I S O R : D O N A L D R A I N N I E , P H . D
THE ROLE OF DOPAMINE
IN FEAR LEARNING
BACKGROUND- PTSD & DOPAMINE
(DA)
• Posttraumatic Stress Disorder (PTSD) is an anxiety
disorder that develops after a traumatic event.
• Dysfunctional dopaminergic signaling is thought to cause
several psychiatric disorders (anxiety disorder, ASD,
schizophrenia, etc.)
• These conditions are associated with attention
processing, learning and memory, and emotion
• Abnormal dopaminergic signaling could have a critical
impact on the circuitry that regulates normal behavior.
DA & FEAR
• During the formation of fear, there is increased activity in
the basolateral amygdala (BLA)- this is fundamental for
the normal function of the BLA.
• Fear memory formation cannot occur without DA present
• Abnormalities in BLA signaling or DA transmission
results in abnormal fear responses which lead to anxiety
disorders.
DA, FEAR, &PKA
• D1- PKA
cascade in BLA
principle
neurons could
be critical for
the formation of
fear memories.
• Inhibition of this
cascade stops
fear learning.
From Dr. Rainnie
HYPOTHESIS
• D1 receptor
antagonist SCH
23390 will inhibit
the PKA pathway,
which inhibits the
learning of a fear.
METHODS
http://www.intechopen.com/source/html/41579/media/image1_w.jpg
From Dr. Rainnie
METHODS
Kilts & Anderson, 1987, Inoue et. al., 1994 & Inglis & Moghaddam, 1999, Floresco and Tse, 2007
BARPRESSING SUPRESSION RATIO (BSR)
BSR= Barpressing Before Tone- Barpressing During Tone
Barpressing Before Tone+ Barpressing During Tone
• Total suppression= 1
• No suppression= 0
• This ratio expresses the change in response rate in
relation to hearing the tone after fear conditioning.
RESULTS- BARPRESS DATA
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
MeanBSR+/-SEM
Saline
D1 Antagonist
P value:
0.0002
N= 6 per
group
***
RESULT- FREEZING DATA
N= 6 per
group
0
10
20
30
40
50
60
D1 antagonist saline
DurationPercentage(%)
DISCUSSION
• Injection of SCH 23390 inhibited the recall of the fear
conditioning.
• Results suggest that D1 receptor antagonist injection
blocks the PKA cascade, thereby disrupting the
communication of the mPFC and the BLA.
• This evidence may help identify novel points of
intervention for the treatment of anxiety disorders
through DA modulation.
FUTURE DIRECTIONS
• In the future, data analysis of electrophysiology to
explain the communication of the mPFC and the BLA
during the acquisition of fear learning.
Prefrontal Cortex
Amygdala
http://www.clker.com/cliarts/w/6/Q/z/2/6/outline-of-brain.svg
ACKNOWLEDGEMENTS
• Dr. Donald “Tig” Rainnie, Ph. D.
• Dr. Teresa Madsen, Ph.D.
• Jeffrey Hsu
• Rainnie Lab
• NET/work Directors, Coordinators, & Cohorts
• Yerkes Primate Research Center, Emory University

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DA&FL

  • 1. J A M I L A P I T T S , J E F F R E Y H S U , T E R E S A M A D S E N , P H . D , A D V I S O R : D O N A L D R A I N N I E , P H . D THE ROLE OF DOPAMINE IN FEAR LEARNING
  • 2. BACKGROUND- PTSD & DOPAMINE (DA) • Posttraumatic Stress Disorder (PTSD) is an anxiety disorder that develops after a traumatic event. • Dysfunctional dopaminergic signaling is thought to cause several psychiatric disorders (anxiety disorder, ASD, schizophrenia, etc.) • These conditions are associated with attention processing, learning and memory, and emotion • Abnormal dopaminergic signaling could have a critical impact on the circuitry that regulates normal behavior.
  • 3. DA & FEAR • During the formation of fear, there is increased activity in the basolateral amygdala (BLA)- this is fundamental for the normal function of the BLA. • Fear memory formation cannot occur without DA present • Abnormalities in BLA signaling or DA transmission results in abnormal fear responses which lead to anxiety disorders.
  • 4. DA, FEAR, &PKA • D1- PKA cascade in BLA principle neurons could be critical for the formation of fear memories. • Inhibition of this cascade stops fear learning. From Dr. Rainnie
  • 5. HYPOTHESIS • D1 receptor antagonist SCH 23390 will inhibit the PKA pathway, which inhibits the learning of a fear.
  • 7. METHODS Kilts & Anderson, 1987, Inoue et. al., 1994 & Inglis & Moghaddam, 1999, Floresco and Tse, 2007
  • 8. BARPRESSING SUPRESSION RATIO (BSR) BSR= Barpressing Before Tone- Barpressing During Tone Barpressing Before Tone+ Barpressing During Tone • Total suppression= 1 • No suppression= 0 • This ratio expresses the change in response rate in relation to hearing the tone after fear conditioning.
  • 10. RESULT- FREEZING DATA N= 6 per group 0 10 20 30 40 50 60 D1 antagonist saline DurationPercentage(%)
  • 11. DISCUSSION • Injection of SCH 23390 inhibited the recall of the fear conditioning. • Results suggest that D1 receptor antagonist injection blocks the PKA cascade, thereby disrupting the communication of the mPFC and the BLA. • This evidence may help identify novel points of intervention for the treatment of anxiety disorders through DA modulation.
  • 12. FUTURE DIRECTIONS • In the future, data analysis of electrophysiology to explain the communication of the mPFC and the BLA during the acquisition of fear learning. Prefrontal Cortex Amygdala http://www.clker.com/cliarts/w/6/Q/z/2/6/outline-of-brain.svg
  • 13. ACKNOWLEDGEMENTS • Dr. Donald “Tig” Rainnie, Ph. D. • Dr. Teresa Madsen, Ph.D. • Jeffrey Hsu • Rainnie Lab • NET/work Directors, Coordinators, & Cohorts • Yerkes Primate Research Center, Emory University