Antidepressant-like effects of 1-aminocyclopropanecarboxylic acid and d-cycloserine in an animal model of depression

Abstract

Antidepressant activity of partial agonists at strychnine-insensitive glycine receptors, l-aminocyclopropanecarboxylic acid (ACPC) and d-cycloserine, was studied in a chronic mild stress model of depression. In this model, a substantial decrease in consumption of a palatable sucrose solution is observed over time in rats subjected to a variety of mild stressors. This decrement can be reversed by chronic administration of antidepressant drugs. Chronic (5 weeks) treatment with ACPC gradually reversed chronic mild stress-induced reductions in sucrose consumption, and the magnitude of this effect was comparable to that observed following similar administration of imipramine (10 mg/kg). The time-course for reversal of chronic mild stress-induced deficits in sucrose consumption by ACPC was dose-dependent. Thus, the first statistically significant effect of the low dose of ACPC (100 mg/kg) was observed after four weeks of treatment (comparable to the 3–5 weeks required for imipramine), while only two weeks of treatment was required in the group receiving a higher dose (200 mg/kg) of ACPC. Like imipramine, reversal of chronic mild stress-induced deficits in sucrose consumption by ACPC persisted for at least one week following cessation of treatment. The effects of chronic d-cycloserine were variable, and apparently not dose-related in the chronic mild stress model. d-cycloserine (10 mg/kg) increased sucrose intake in stressed animals, but the magnitude of this effect was smaller than in either imipramine or ACPC treated animals. Lower (2.5 mg/kg) and higher (40, 100 mg/kg) doses of d-cycloserine were ineffective. These results suggest that ACPC may have antidepressant properties comparable to conventional drugs, but with a faster onset of action.