Role of the 5HT2C receptor in anxiety-like behavior in zebrafish (Danio rerio)

The present study aims to describe the acute effects of 5-HT 2C receptor agonists and antagonists in behavioral tests related to anxiety in adult zebrafish ( Danio rerio ). For this, three groups of fish ( n = 12/group) were used: a group treated with the drug MK-212 (2 mg/kg), a 5-HT 2C receptor agonist; another group treated with the drug RS-102221 (2 mg/kg), a 5-HT 2C receptor antagonist; and a third group, the control group, using a vehicle solution. The three groups were exposed to two behavioral tests: novel tank test (NTT) and light-dark preference (LDT). MK-212 produced no effects on the NTT, while RS-102221 decreased geotaxis (d = 0.99, 95%CI[0.3, 1.7]) and erratic swimming (d = 0.87, 95%CI[0.18, 1.56]) in this test; these effects are consistent with a tonic facilitation of defensive behavior in the NTT. Conversely, in the LDT, MK-212 increased scototaxis (d = 0.96, 95%CI[0.25, 1.65]), risk assessment (d = -1.31, 95%CI[-2.02, -0.59]), and thigmotaxis (d = -1.48, 95%CI[-2.21, -0.75]), consistent with an anxiogenic-like effect of this drug. Thus, tonic and phasic effects of the activation of this receptor are observed depending on the type of behavioral test used.