Antidepressant-like effect by postsynaptic 5-HT1A receptor activation in mice.

The antidepressant-like effect of 5-(3(-)[((2S)-1,4-benzodioxan-2-ylmethyl)amino]propoxy)-1,3- benzodioxole (MKC-242), a novel 5-HT1A receptor agonist, was studied in the forced swimming test in mice injected i.c.v. with 5,7-dihydroxytryptamine to destroy 5-HT neurons or treated with p-chlorophenylalanine to inhibit 5-HT synthesis. MKC-242 reduced immobility time of mice pretreated with vehicle and these drugs, although it did not affect their locomotor activity. The anti-immobility effect was antagonized by 5-HT1A receptor antagonists such as propranolol and N-tert-butyl-3-(4-(2-methoxyphenyl)piperazin-1-yl)-2-phenylpropana mide. These findings support the hypothesis that postsynaptic 5-HT1A receptors play an important role in the antidepressant-like effect of 5-HT1A receptor agonists.