MK-801 and enantiomers: potential antidepressants or false positives in classical screening models?

In the present experiments, the noncompetitive NMDA antagonist 5-methyl-10,11-dihydroxy-5H-dibenzo(a,d)cyclo-hepten-5,10-imine (MK-801) and its (+) and (-) enantiomers were tested in classical screening models used to detect potential antidepressants. The drug and its enantiomers were active in the tail suspension test (TST). The racemate was also active in the forced swimming test (FST). The effects in these tests occurred, however, at doses with marked stimulant activity. Further investigations (reserpine, apomorphine, and yohimbine tests) could not confirm the suspected antidepressant activity. Other NMDA antagonists--2-amino-7-phosphonoheptanoic acid (AP7), kynurenic acid, and 1-glutamic acid diethylester (GDEE)--showed no activity in the TST. These findings throw doubt concerning the potential antidepressant activity of MK-801 and other NMDA antagonists.