| dc.description.abstract |
To investigate the antidepressant‑like effect of N‑(benzo[d] thiazol‑2‑yl)‑3‑
ethoxyquinoxalin‑2‑carboxamide 6k, a 5‑hydroxytryptamine type 3 (5‑HT3) receptor antagonist using rodents
behavioral battery tests. Materials and Methods: 6k screening was performed with behavioral assays for
depression‑like forced swim test (FST) at several single doses (0.25-4 mg/kg, intraperitoneal injection (i.p.))
to test the potency of 6k, in which 2 and 4 mg/kg doses were found to be most effective and hence, in further
behavioral assays including mechanistic model like 5‑hydroxytryptophan (5‑HTP)‑induced head twitches
was performed in mice at acute doses of 6k (2 and 4 mg/kg, i.p.). Furthermore, olfactory bulbectomy (OBX),
a surgical model‑induced behavioral alterations was performed in rats, and the effect of 6k administered
orally (2 and 4 mg/kg, p.o.) after subchronic treatment for 14 days starting from day 15 of postsurgery was
examined by percent sucrose preference test and modified open field test (OFT). Results: 6k (1, 2, and
4 mg/kg, i.p.) reduced the immobility time and increased the swimming behavior in FST without affecting
the baseline locomotor score showing antidepressant‑like effect. 5‑HTP‑induced head twitch response
was potentiated by 6k (2 and 4 mg/kg, i.p.), which indicated rise in the serotonergic neurotransmission in
the brain. 6k (2 and 4 mg/kg, p.o.) showed anti‑anhedonia effect by increasing the sucrose consumption
and reversed the behavioral alterations when exposed to modified open field in OBX rats after subchronic
treatment for 14 days, thus exhibiting antidepressant‑like effect. Conclusion: 6k attenuated the behavioral
derangement in rodents‑based behavioral battery tests for depression, indicating antidepressant‑like potential. |
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