Facilitation of conditioned fear extinction by d-cycloserine is mediated by mitogen-activated protein kinase and phosphatidylinositol 3-kinase cascades and requires de novo protein synthesis in basolateral nucleus of amygdala

Yang, Yi; Lu, Kwok-Tung

doi:10.1016/j.neuroscience.2005.04.003

Cited by 91 publications

(80 citation statements)

References 37 publications

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“…A large literature indicates amygdaloid glutamate NMDA receptors play an essential role in the extinction of fear memory (Walker et al, 2002;Ledgerwood et al, 2003Ledgerwood et al, , 2004Yang and Lu, 2005). In the present study, we found that either systemic or intraamygdala administration of glutamate NMDA receptor antagonists (7)-HA966 and MK801 blocked the facilitatory effect of DEX on extinction significantly.…”

Section: Amygdaloid Glutamate Nmda Receptors Participate In the Modulsupporting

confidence: 63%

“…Extinction of the conditioned fear was measured using the well-established fear potentiated startle paradigm (Cassella and Davis, 1986;Lu et al, 2001;Walker et al, 2002;Yang and Lu, 2005;Yang et al, 2006). Rats were trained and tested in a startle chamber (San Diego Instruments, San Diego, CA, USA), in which cage movement results in the displacement of an accelerometer.…”

Section: Behavioral Proceduresmentioning

confidence: 99%

“…Recent studies indicate that glutamate NMDA receptors in the amygdala play a critical role in the extinction of conditioned fear (Walker et al, 2002;Ledgerwood et al, 2003Ledgerwood et al, , 2004Yang and Lu, 2005). This experiment assessed the role of amygdaloid NMDA receptors in the DEX effect, two glutamate NMDA receptor antagonists (7)-HA966 and MK801 were used.…”

Section: Experiments Three: Dex Facilitation Effect On Extinction Was mentioning

confidence: 99%

“…Results demonstrated that either systemic injection of (7) ( Figure 3b). It has been shown that administration of MK801 and (7)-HA966 prior to extinction training blocked extinction (Baker and Azorlosa, 1996;Walker et al, 2002;Yang and Lu, 2005). Thus, it is difficult to conclude that the effect of (7)-HA-966 and MK801 on DEX's facilitatory effect is caused by a disruption of facilitation as opposed to a direct blockade of extinction itself.…”

Section: Experiments Three: Dex Facilitation Effect On Extinction Was mentioning

confidence: 99%

“…These results suggest that brain glucocorticoids may be involved in the dysregulation of fear memory extinction in PTSD patients. Evidence also indicated that administration of the partial NMDA receptor agonist D-cycloserine (DCS) facilitated extinction of conditioned fear (Walker et al, 2002;Ledgerwood et al, 2003Ledgerwood et al, , 2004Ressler et al, 2004;Yang and Lu, 2005) and numerous signaling cascades are involved in the DCS effect on extinction that include mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI-3 kinase) and calcineurin (Yang and Lu, 2005). The amygdaloid NMDA receptors may be also involved in the facilitatory effect of glucocorticoids on the extinction.…”

Section: Introductionmentioning

confidence: 99%

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Glutamate NMDA Receptors within the Amygdala Participate in the Modulatory Effect of Glucocorticoids on Extinction of Conditioned Fear in Rats

Yang

Chao

et al. 2006

Neuropsychopharmacol

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Recent results show that brain glucocorticoids are involved in the dysregulation of fear memory extinction in post-traumatic stress disorder patients. The present study was aimed to elucidate the possible mechanism of glucocorticoids on the conditioned fear extinction. To achieve these goals, male SD rats, fear-potentiated startle paradigm, and Western blot were used. We found that (1) systemic administration of the synthetic glucocorticoid agonist dexamethasone (DEX) facilitated extinction of conditioned fear in a dose-dependent manner (0.05, 0.1, 0.5, or 1.0 mg/kg, i.p.); (2) systemic administration of the glutamate NMDA receptor antagonist (7)-HA966 (6.0 mg/kg, i.p.) and intra-amygdala infusion of the NMDA receptor antagonists MK801 (0.5 ng/side, bilaterally) or D,L-2-amino-5-phosphonovaleric acid (AP5, 2.0 ng/side, bilaterally) blocked the DEX facilitation effect; (3) the corticosteroid synthesis inhibitor metyrapone (25 mg/kg. s.c.) blocked extinction and this was prevented by co-administration of NMDA receptor agonist D-cycloserine (DCS, 5.0 mg/kg, i.p.); (4) co-administration of DEX and DCS in subthreshold doses provided a synergistic facilitation effect on extinction (0.2 and 5 mg/kg, respectively). Control experiments indicated that co-administration of DEX and DCS did not alter the expression of conditioned fear and the effect was not due to lasting damage to the amygdala. These results suggest that glutamate NMDA receptors within the amygdala participate in the modulatory effect of glucocorticoids on extinction.

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Section: Amygdaloid Glutamate Nmda Receptors Participate In the Modulsupporting

confidence: 63%

Section: Behavioral Proceduresmentioning

confidence: 99%

Section: Experiments Three: Dex Facilitation Effect On Extinction Was mentioning

confidence: 99%

Section: Experiments Three: Dex Facilitation Effect On Extinction Was mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Glutamate NMDA Receptors within the Amygdala Participate in the Modulatory Effect of Glucocorticoids on Extinction of Conditioned Fear in Rats

Yang

Chao

et al. 2006

Neuropsychopharmacol

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Augmentation of psychotherapy with d-cycloserine for anxiety disorders

Ipser

Sander

Seifan

et al. 2009

Cochrane Database of Systematic Reviews

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Augmentation of cognitive and behavioural therapies (CBT) with d-cycloserine for anxiety and related disorders

Ori

Amos

Bergman

et al. 2015

Cochrane Database of Systematic Reviews

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Facilitation of conditioned fear extinction by d-cycloserine is mediated by mitogen-activated protein kinase and phosphatidylinositol 3-kinase cascades and requires de novo protein synthesis in basolateral nucleus of amygdala

Cited by 91 publications

References 37 publications

Glutamate NMDA Receptors within the Amygdala Participate in the Modulatory Effect of Glucocorticoids on Extinction of Conditioned Fear in Rats

Glutamate NMDA Receptors within the Amygdala Participate in the Modulatory Effect of Glucocorticoids on Extinction of Conditioned Fear in Rats

Augmentation of psychotherapy with d-cycloserine for anxiety disorders

Augmentation of cognitive and behavioural therapies (CBT) with d-cycloserine for anxiety and related disorders

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