Tolerance to anxiolytic- and antidepressant-like effects of a partial agonist of glycine(B) receptors

The present study examined effects of acute and repeated administration of 1-aminocyclopropanecarboxylic acid (ACPC), a partial agonist of glycine, re ceptors, in the conflict drinking test and the forced swim test in rats. Di azepam and imipramine were used, respectively, as reference drugs in those tests. In the conflict drinking test, acute administration of ACPC (200 mg/ kg) increased fivefold the number of punished licks. A three- and fivefold increase in the number of punished licks was observed in rats treated repea tedly with ACPC (200 mg/kg daily; 14 days) and challenged with the same dos e of the drug 24 h or 4 days later, respectively. A single injection of ACP C (400 mg/kg) reduced by 40% the immobility time in the forced swim test. I n rats treated repeatedly with ACPC (400 mg/kg daily; 14 days) and challeng ed with the same dose 24 h or 4 days later, the drug either produced no sig nificant effect or reduced the immobility time by 50%, respectively. On the other hand, no changes in anxiolytic- and antidepressant-like effects of c hronically administered diazepam (10 mg/kg daily; 14 days) and imipramine ( 30 mg/kg daily; 14 days), respectively, were observed. The above results in dicate that tolerance develops to the anxiolytic- and, particularly, to the antidepressant-like activity of ACPC. (C) 1999 Elsevier Science Inc.