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.
Matsuda
T
T
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Osaka University, Japan.
Somboonthum
P
P
Suzuki
M
M
Asano
S
S
Baba
A
A
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D003863:Depression / Q000523:psychology; D004146:Dioxanes / Q000494:pharmacology*; D004149:Dioxoles / Q000494:pharmacology*; D010134:Fenclonine / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D018490:Serotonin Agents / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013550:Swimming
D000928:Antidepressive Agents; D004146:Dioxanes; D004149:Dioxoles; D017981:Receptors, Neurotransmitter; D018490:Serotonin Agents; D017366:Serotonin Receptor Agonists; D015116:5,7-Dihydroxytryptamine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C096294:osemozotan; D010134:Fenclonine