D-Cycloserine accelerates the extinction of cocaine-induced conditioned place preference in C57bL/c mice

Abstract

Recently, it was shown that d-cycloserine (DCS, a NMDA partial agonist) facilitated extinction of fear as well as cocaine conditioned place preference (CPP) in rats. Methods The present study examined the effects of DCS (15 mg/kg i.p. and 30 mg/kg i.p.) on extinction and renewal of cocaine-induced CPP in C57bL/c mice. In parallel, we examined the effects of DCS on locomotor activity. Results Extinction to cocaine CPP was significantly faster with DCS than with vehicle treatment (three versus six sessions, respectively). After extinction was achieved, mice were retested for CPP 1 and 2 weeks later. All animals maintained extinction to CPP 1 week later, but at 2 weeks, the vehicle and the 15 mg/kg DCS-treated animals maintained the extinction, but the 30 mg/kg DCS-treated mice had renewed CPP. During induction of cocaine CPP, mice displayed enhanced locomotor activity following treatment with cocaine, as expected, based on previous literature. During extinction, there were no differences in locomotor activity between the vehicle and the 15 mg/kg DCS-treated mice, whereas the 30 mg/kg DCS-treated animal showed significant locomotor activity inhibition. These results corroborate in mice the previously reported acceleration of extinction to cocaine-induced CPP by DCS in rats. However, we also show that the higher DCS doses facilitated CPP reestablishment after extinction. Thus, while DCS could be beneficial in accelerating the extinction to conditioned responses in addiction it could, at higher doses, increase the risk of relapse. Thus, studies evaluating the beneficial therapeutic effects of DCS should assess not only the short-term effects but also the potential of longer lasting undesirable effects.