Anticonflict effect of the glycineB receptor partial agonist, D-cycloserine, in rats. Pharmacological analysis

Rationale: Several studies have provided evidence that antagonists and partial agonists of glycineB receptors exhibit an anxiolytic-like activity in different animal models. Objective: Using the conflict-drinking Vogel test in rats as a model, in the present study we examined the anxiolytic-like activity of D-cycloserine (DCS), a partial agonist of the glycineB site of the N-methyl-D-aspartate (NMDA) receptor complex. Diazepam was used as a reference drug. Results: DCS (200 and 300 mg/kg) and diazepam (5 mg/kg) produced an anxiolytic-like effect in rats by increasing the number of shocks accepted. We also demonstrated that NMDA (15 mg/kg) reduced the anxiolytic-like activity of DCS (200 mg/kg), whereas glycine (800 mg/kg) and flumazenil (10 mg/kg) did not affect the anticonflict effect of DCS (200 mg/kg). The anticonflict effect of diazepam (5 mg/kg) was totally blocked by flumazenil (10 mg/kg). Conclusion: The obtained results have shown that DCS exhibits an anxiolytic-like activity which depends on NMDA receptors rather than on glycineB or benzodiazepine sites.