Abstract
The adenylyl cyclase (AC) pathway is involved in the pathophysiology of depression. Finding new antidepressants with high medicinal properties and low side effects is warranted. Therefore, this study was designed to determine the antidepressant-like effect of tropisetron on a maternal separation (MS) model in mice, considering the possible role of AC. NMRI male mice were divided into eleven groups. The control group was treated with saline and MS groups were treated with saline, tropisetron (a 5-HT3 receptor antagonist) at doses of 1, 3, and 5 mg/kg; forskolin (an activator of AC) at doses of 5, 10, and 25 mg/kg; a subeffective dose of forskolin with a subeffective dose of tropisetron; and an effective dose of tropisetron plus an effective dose of NB001 (3 mg/kg) (an AC inhibitor). After treatment, animals were subjected to behavioral tests including the forced swimming test (FST), splash test, and open field test (OFT). We showed that MS caused depressive-like behaviors determined as an increase in the immobility time in the forced swimming test (FST) and decreased grooming time in the splash test. Our results showed that administration of tropisetron, as well as forskolin, mitigated the depressive-like behaviors in MS mice. We found that coadministration of a subeffective dose of tropisetron plus a subeffective dose of forskolin potentiated the antidepressant-like effect of tropisetron. However, coadministration of an effective dose of NB001 with an effective dose of tropisetron did not significantly affect the antidepressant-like effect of tropisetron. We concluded that the antidepressant-like effects of tropisetron on MS mice are partially mediated through the adenylyl cyclase pathway.
Highlights
Depression is one of the most common psychological disorders [1]
Results of the present study showed that maternal separation (MS) provoked depressive-like behaviors in the forced swimming test (FST) and splash test as the increase in the immobility time and the decrease in the grooming activity time, respectively
Our findings are in agreement with previous studies and determined that the MS causes depressive-like behaviors in the FST and splash test, as immobility time in MS mice increased in the FST test and the self-care and self-cleaning times significantly decreased in the splash test
Summary
Depression is one of the most common psychological disorders [1]. More than 15% of people experience at least one period of depression in developed countries in their lifetime [2, 3]. Monoamine serotonin or 5-hydroxytryptamine (5-HT) is an important neurotransmitter in the pathophysiology of depressive disorder and is involved in the mechanisms of action of commonly used antidepressants [9]. Studies in both animal and clinical models have shown that depression is clearly associated with a decrease in the level of serotonin in the central nervous system (CNS) [10,11,12,13]. Evidence suggests that the 5-HT3 receptor, as ion channel ligands, is involved in brain development and maturation This receptor is widely distributed in the CNS and plays an important role in regulating various processes and different brain functions. Previous studies have shown that the 5-HT3 receptor antagonists, including tropisetron and ondansetron, possessed antidepressant-like
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