Antidepressant and anxiolytic-like effects of 4n, a novel 5-HT3 receptor antagonist using behaviour based rodent models.

The present study was designed to investigate the putative antidepressant and anxiolytic-like effects of N-n-Butylquinoxalin-2-carboxamide (4n), a novel 5-HT3 receptor antagonist, with an optimal log P (2.01) and pA2 value (7.3) greater than ondansetron (6.9) using rodent behavioural models of depression and anxiety. Acute treatment of 4n (1-4 mg/kg, ip) in mice produced antidepressant-like effect in forced swim test (FST) without affecting the baseline locomotion in actophotometer test in mice. 4n (2-4 mg/kg, ip) treatment also potentiated the 5-hydroxytryptophan (5-HTP) induced head twitch response in mice. Further, 4n (1-4 mg/kg, ip) treatment antagonized reserpine induced hypothermia in rats. Chronic treatment (14 days) with 4n (1-4 mg/kg) and paroxetine (10 mg/kg) significantly attenuated the behavioural anomalies induced by bilateral olfactory bulbectomy in rats in modified open field paradigm. An anxiogenic-like behaviour was induced by light alone as the stimulus using light-dark aversion test. 4n (2-4 mg/kg, ip) treatment significantly increased no. of transitions between dark and lit area and the time spent in the lit area. In conclusion, these preliminary investigations confirm that 4n exhibited antidepressant and anxiolytic-like effects in rodent models of depression and anxiety.

Effect of anti-depressants on neuro-behavioural consequences following impact accelerated traumatic brain injury in rats.

Disruption of normal neuronal networks and neurotransmitters like serotonin and norepinephrine levels in post traumatic brain injury (TBI) are observed to be the primary causative agent for depression/anxiety. This communication reports the efficacy of various classes’ anti-depressants in the treatment of depression/anxiety following TBI in rats. Chronic treatment with anti-depressants (escitalopram and venlafaxine) leads to improvement in the depressive/anxiogenic -like behaviour in the TBI rat and corroborates the notion of the involvement of serotonin and norepinephrine in the behavioural consequences of post-TBI. Chronic treatments with escitalopram and venlafaxine significantly reversed the effect of TBI as compared to vehicle-treated TBI group. The results showed a quantitative battery of neuro-behavioural functional assessments that correlates with neuronal damage following traumatic brain injury.