Anticonflict effect of the glycineB receptor partial agonist, D-cycloserine, in rats. Pharmacological analysis.
BACKGROUND
Several studies have provided evidence that antagonists and partial agonists of glycine(B) 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 glycine(B) 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).


CONCLUSIONS
The obtained results have shown that DCS exhibits an anxiolytic-like activity which depends on NMDA receptors rather than on glycine(B) or benzodiazepine sites.
Klodzińska
A
A
Institute of Pharmacology, Polish Academy of Sciences, Smetna. klodzin@if-pan.krakow.pl
Chojnacka-Wójcik
E
E
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D003220:Conflict, Psychological; D003523:Cycloserine / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005442:Flumazenil / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018009:Receptors, Glycine / Q000819:agonists*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology
D014151:Anti-Anxiety Agents; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D005442:Flumazenil; D003523:Cycloserine; D003975:Diazepam