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

Oliveira, L. N.; Souza, L. V. X. d. B.; Bozi, B. S.; Costa, B. P. D.; Pantoja, A. R. B.; Lima-Maximino, M.; Ripardo, R. C.; Maximino, C.

doi:10.1101/2025.07.11.664334

bioRxiv · 10.1101/2025.07.11.664334

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

Oliveira, L. N.·Souza, L. V. X. d. B.·Bozi, B. S.·Costa, B. P. D.·Pantoja, A. R. B.·Lima-Maximino, M.·Ripardo, R. C.·Maximino, C.

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Abstract

The present study aims to describe the acute effects of 5-HT2C 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-HT2C receptor agonist; another group treated with the drug RS-102221 (2 mg/kg), a 5-HT2C 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.

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Oliveira, L. N., Souza, L. V. X. d. B., Bozi, B. S., Costa, B. P. D., Pantoja, A. R. B., Lima-Maximino, M., Ripardo, R. C., Maximino, C.. 2025-07-15. Role of the 5HT2C receptor in anxiety-like behavior in zebrafish (Danio rerio). https://doi.org/10.1101/2025.07.11.664334

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