Agomelatine is a 5HT2C receptor antagonist. Hyperfunction of brain 5HT2C receptor is suggested to be involved in anxiety. The effect of agomelatine was explored in some acute and chronic behavioural models of anxiety. The models used for studying acute anxiety were elevated plus maze (EPM), hole board test (HBT), open field test (OFT), light/dark exploration (LDA) and marble burying test (MBT). Agomelatine (1, 10 and 30 mg/kg, i.p) and meta-chlorophenyl piperazin (m-CPP) (1\nmg/kg, i.p) were used for acute study. The effects of chronic administration of agomelatine (1, 10 and 30 mg/kg, p.o for 15 days) were investigated on two different anxiety models, the elevated T-maze and open field test. Cumulative Concentration Response Curve (CCRC) of 5HT2 was plotted using mice fundus at the end of treatment schedule. In acute study, agomelatine significantly (p<0.05) increased the time spent, number of entries in open arms, number of head dips and rearings, number of squares travelled, the time spent in light box, no. of transitions and number of marbles buried as compared to control in EPM, HBT, OFT, LDA and MBT respectively. Agomelatine significantly reversed the effects of m-CPP (1 mg/kg, i.p). In chronic study, agomelatine significantly (p<0.05) impaired inhibitory avoidance and facilitated escape latency and did not impair locomotion in open field test. CCRC of 5-HT2 was shifted towards the right with suppression of maxima in mice treated with agomelatine. The present investigation demonstrates that agomelatine has value in the treatment of acute anxiety states as well as in generalised anxiety disorders and panic disorders.
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