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

0.05

0.1

0.15

0.2

0.25

0.3

0.35

0.4

0.45

0.5

Saline

D1 Antag-onist

Mea

n BS

R +

/- S

EM

P value: 0.0002N= 6 per group

***

RESULT- FREEZING DATA

N= 6 per group

D1 antagonist saline0

5

10

15

20

25

30

35

40

Dur

atio

n Pe

rcen

tage

(%

)

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 CortexAmygdal

ahttp://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