The facilitative effects of d-cycloserine on extinction of a cocaine-induced conditioned place preference can be long lasting and resistant to reinstatement

Rationale and objective: The N-methyl-d-aspartate receptor agonist, d-cycloserine (DCS), accelerates extinction of a cocaine-induced conditioned place preference (CPP) when given after daily extinction tests. Here, we studied the effects of DCS in rats given spaced-extinction sessions at 3- or 7-day intervals using two different extinction procedures. Materials and methods: Rats were trained on a CPP (four cocaine, 10 mg/kg, i.p., and four saline pairings with one of two compartments). Immediately following the CPP test and all extinction tests (days 4, 7, 10, and 24, experiment 1), DCS (15 mg/kg, i.p.) or saline was administered. In experiment 2, extinction was conducted by exposing rats to the drug-paired cues for 2 or 20 min, three times, at 7-day intervals followed immediately by DCS or saline. After extinction, tests for retention and cocaine-induced reinstatement were given. Results: In experiment 1, rats given DCS lost the cocaine CPP after one extinction trial, an effect that persisted for 2 weeks after the last DCS injection and that was resistant to cocaine-induced reinstatement. In experiment 2, extinction was facilitated by DCS compared to saline when rats received 2-min exposures to the conditioned stimulus. Longer 20-min exposures minus/plus repeated testing led to retention of extinction in both groups regardless of DCS treatment. Conclusions: Extinction of appetitive conditioning is facilitated by DCS after 1-3 post-spaced trial injections, and retention is lasting and resistant to reinstatement. The facilitative effects appear early in extinction, but when extinction procedures are intensive, DCS appears to have no additional benefit.