Indomethacin, a nonselective cyclooxygenase inhibitor, does not interact with MTEP in antidepressant-like activity, as opposed to imipramine in CD-1 mice

Abstract

The contribution of metabotropic glutamate receptors (mGlu receptors) in depression is well known and tested worldwide. Our previous study showed the involvement of the cyclooxygenase-2 (COX-2) pathway in behavioral changes mediated by an antagonist of metabotropic glutamate receptor subtype 5 (mGlu5 receptor) 3-[(2-methyl-1,3-tiazol-4-yl)ethynyl]-pyridine (MTEP). Among others, we have found that chronic concomitant administration of a COX-2 inhibitor and sub-effective dose of MTEP accelerates antidepressant-like activity of MTEP. This paper seeks to explore whether the same effect would be observed with the use of a non-selective COX inhibitor 2-[1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]acetic acid (indomethacin). To that end, we have employed experimental procedure implemented in the earlier research. MTEP and indomethacin or MTEP + indomethacin were used chronically for 7 or 14 days. Then, the Porsolt test, tail suspension test and locomotor activity test were performed. Imipramine was used as a reference compound, as its action is connected with mGlu5 receptor. We found that, in contrast to COX-2 inhibition, indomethacin – acting both through COX-1 and COX-2 – did not release antidepressant-like potential of MTEP. The opposite effect was shown when imipramine was used.