Effects of D-Cycloserine on Extinction: Consequences of Prior Exposure to Imipramine

Background D-cycloserine (DCS), a partial N-methyl-d-aspartate (NMDA) agonist, facilitates the extinction of conditioned fear in animals and promotes the efficacy of exposure-based therapies in humans. The current study examined whether pre-exposure to the antidepressant imipramine affects the enhancement of extinction by DCS. Methods Twenty-nine rats were pre-exposed to saline, DCS, or imipramine for 14 days. The next day they were given five noise-shock pairings. The day after training, rats received six extinction trials and were then injected with DCS. At test the following day, freezing elicited by the noise was measured. Results Rats pre-exposed to either DCS or imipramine exhibited more freezing at test than rats pre-exposed to saline. Conclusions Chronic exposure to either DCS or imipramine prevents the facilitating effect of DCS on extinction. This result suggests that DCS may not effectively enhance loss of fear in patients who are also being treated with antidepressants.