1. ¹Institute of Biotechnology, National Chia-Yi University, Chia-Yi, Taiwan
2. ²Department of Life Science, National Taiwan Normal University, Taipei, Taiwan
3. ³Second Department of Neurology, Chang Gung Memorial Hospital and Chang Gung University, Taipei, Taiwan

Correspondence: Dr K-T Lu, Department of Life Science, National Taiwan Normal University, 88 Ting-Chow Road, Sec 4, Taipei, Taiwan. Tel: +886 2 29333149 ext. 234; Fax: +886 2 29312904; E-mail: ktlu@ntnu.edu.tw

Received 1 November 2005; Revised 3 August 2006; Accepted 24 August 2006; Published online 18 October 2006.

Abstract

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 ()-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.