Anxiolytic-like effect of natural product 2-hydroxy-3,4,6-trimethoxyacetophenone isolated from Croton anisodontus in adult zebrafish via serotonergic neuromodulation involvement of the 5-HT system

Abstract

Benzodiazepines are highly effective in combating anxiety; however, they have considerable adverse effects, so it is important to discover new safe anxiolytic agents. This study was designed to investigate the anxiolytic and anticonvulsant effect of natural product 2-hydroxy-3,4,6-trimethoxyacetophenone (HTMCX) and its possible mechanisms of action in adult zebra sh. The open eld and light / dark tests (n = 6 animals/group) were used to assess anxiety and pentylenetetrazole (PTZ) as a seizure inducer. The 96-hour acute toxicity of HTMCX was also investigated. HTMCX (1, 3, and 10 mg / Kg; v.o.) was not toxic and affected locomotor activity. The highest doses (3 and 10 mg / Kg; v.o.) produced signs of anxiolytic action in the light / dark test, and this effect was abolished by the pizotifen (antagonist 5HTR1 and 5HTR2A / 2C), having the potential to form a complex in the same region of the site indicating that the anxiolytic effect via the serotonergic mechanism. However, the anxiolytic effect of HTMCX has not been abolished by umazenil (antagonist GABAR A ), cyproheptadine (antagonist 5HTR2A), and granisetron (antagonist 5HTR3A / 3B). Therefore, HTMCX demonstrated an anxiolytic effect, suggesting that the 5HTR1 and 5HTR / 2C receptors may be involved in the pharmacological performance of this acetophenone in the central nervous system.

N-acetylcysteine and acetyl-L-carnitine did not prevent acute PTZ-induced seizure in adult and larvae zebrafish

“…Our study showed that diazepam effectively increased latency for the highest seizure scores and reduced seizure intensity at concentrations of 50 µM (adults) and 18 µM (larvae) in zebrafish. These results support other studies where diazepam was used as a positive control to reduce seizures induced by PTZ in zebrafish (Choo et al, 2018;da Silva et al, 2021).…”