Source Paper
Facilitation of Conditioned Fear Extinction by Systemic Administration or Intra-Amygdala Infusions of d-Cycloserine as Assessed with Fear-Potentiated Startle in Rats
David L. Walker, Kerry J. Ressler, Kwok-Tung Lu, Michael Davis
Journal of Neuroscience • 2002
Fear Conditioning
Objective: To evaluate the ability of d-cycloserine (DCS) to facilitate conditioned fear extinction in rats as assessed with fear-potentiated startle
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Protocol Steps
Fear Conditioning
Rats received pairings of a light stimulus and footshock to establish conditioned fear responses
Note: 10 pairings total with 3.7 second light and 0.4 mA footshock
View evidence from paper
“Rats received 10 pairings of a 3.7 sec light and a 0.4 mA footshock (fear conditioning)”
Baseline Fear-Potentiated Startle Measurement
Fear-potentiated startle was measured before extinction training to establish baseline responses
Note: Measured as increased startle in presence vs absence of light
View evidence from paper
“Fear-potentiated startle (increased startle in the presence vs the absence of the light) was subsequently measured before and after”
Extinction Training
Rats received non-reinforced light presentations without shock to extinguish the conditioned fear response
Note: Light presented without accompanying footshock
View evidence from paper
“30, 60, or 90 presentations of the light without shock (extinction training)”
Post-Extinction Fear-Potentiated Startle Measurement
Fear-potentiated startle was measured after extinction training to assess extinction learning
Note: Compared to baseline measurements
View evidence from paper
“Fear-potentiated startle (increased startle in the presence vs the absence of the light) was subsequently measured before and after”
DCS Administration (Experiment 2)
DCS was injected systemically before non-reinforced light exposures to test dose-dependent effects on extinction
Note: Three dose levels tested: 3.25, 15, or 30 mg/kg
View evidence from paper
“DCS injections (3.25, 15, or 30 mg/kg) before 30 non-reinforced light exposures dose-dependently enhanced extinction”
DCS Control Test (Experiment 3)
DCS was administered to rats that did not receive extinction training to test for non-specific effects on fear-potentiated startle
Note: Control to verify DCS does not influence startle without extinction training
View evidence from paper
“DCS injections (3.25, 15, or 30 mg/kg) before 30 non-reinforced light exposures dose-dependently enhanced extinction but did not influence fear-potentiated startle in rats that did not receive extinction training”
HA-966 Antagonist Test (Experiment 4)
HA-966 was administered to block the glycine-recognition site and test whether DCS effects are mediated through this site
Note: HA-966 blocked the extinction-enhancing effects of DCS
View evidence from paper
“These effects were blocked by HA-966, an antagonist at the glycine-recognition site”
Pre-Testing Drug Administration (Experiment 5)
DCS or HA-966 were injected before testing to determine if they affect startle measurement itself
Note: Neither drug altered fear-potentiated startle when given before testing
View evidence from paper
“Neither DCS nor HA-966 altered fear-potentiated startle when injected before testing”
Intra-Amygdala DCS Infusion (Experiment 6)
DCS was infused directly into the amygdala before extinction training to test local effects
Note: 10 μg/side dose used; effects mimicked systemic administration
View evidence from paper
“The effect of systemic administration was mimicked by intra-amygdala DCS (10 μg/side) infusions”