Rationale: The involvement of glutamate in fear extinction is perhaps the most promising in terms of facilitating clinical interventions for posttraumatic stress disorder (PTSD). This study was aimed at elucidating the possible role of zif268 on the D-cycloserine (DCS) facilitation effect on extinction. Objective: We investigated the association between zif268 and the extinction of conditioned fear by using antisense oligodeoxynucleotide (ODN) of zif268 and the fear-potentiated startle paradigm. Methods: Male adult Wistar rats were injected DCS (15 mg/kg, IP) 15 min prior to the extinction training, administered with antisense or sense ODN (800 pmol) of zif268 and subjected for fear-potentiated startle paradigm (FPS) and Western blot. Results: Either context exposure or cue exposure elevated the expression of zif268 in the basolateral nucleus of the amygdala (BLA) (p∈<∈0.05 and p∈<∈0.01, respectively) compared to the control group. Additionally, zif268 expression in BLA was further elevated by the glutamate NMDA receptor agonist DCS administration. Intra-amygdaloid injection of the antisense ODN of zif268 blocked the facilitation effect of DCS on the extinction of conditioned fear. Subsequent control experiments indicated that administration of vehicle or zif268 sense ODN did not alter the facilitation of DCS and that the blockage effect of zif268 antisense ODN was not due to lasting damage to the amygdala. Conclusions: Our results suggest that zif268 within the amygdala participates in the DCS facilitation effect on the extinction of conditioned fear.
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