Tolerance to anxiolytic- and antidepressant-like effects of a partial agonist of glycineB receptors.

摘要

The present study examined effects of acute and repeated administration of 1-aminocyclopropanecarboxylic acid (ACPC), a partial agonist of glycineB receptors, in the conflict drinking test and the forced swim test in rats. Diazepam 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 repeatedly with ACPC (200 mg/kg daily; 14 days) and challenged with the same dose of the drug 24 h or 4 days later, respectively. A single injection of ACPC (400 mg/kg) reduced by 40% the immobility time in the forced swim test. In rats treated repeatedly with ACPC (400 mg/kg daily; 14 days) and challenged with the same dose 24 h or 4 days later, the drug either produced no significant effect or reduced the immobility time by 50%, respectively. On the other hand, no changes in anxiolytic- and antidepressant-like effects of chronically administered diazepam (10 mg/kg daily; 14 days) and imipramine (30 mg/kg daily; 14 days), respectively, were observed. The above results indicate that tolerance develops to the anxiolytic- and, particularly, to the antidepressant-like activity of ACPC.