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Anxiolytic-like effect of chalcone N-{(4′-[(E)-3-(4-fluorophenyl)-1-(phenyl) prop-2-en-1-one]} acetamide on adult zebrafish (Danio rerio): Involvement of the GABAergic system

2019; Elsevier BV; Volume: 374; Linguagem: Inglês

10.1016/j.bbr.2019.03.040

1872-7549

Maria Kueirislene Amâncio Ferreira, Antônio Wlisses da Silva, Francisca Crislândia Oliveira Silva, Carlos Leone Alves Holanda, Sheila M. Barroso, Joyce dos Reis Lima, Antônio Eufrásio Vieira Neto, Adriana Rolim Campos, Paulo Nogueira Bandeira, Hélcio Silva dos Santos, Telma L. G. Lemos, Sônia Maria Costa Siqueira, Francisco Ernani Alves Magalhães, Jane Eire Silva Alencar de Menezes,

Nicotinic Acetylcholine Receptors Study

Benzodiazepines are the standard drugs for the treatment of anxiety, but their undesirable side effects make it necessary to develop new anxiolytic drugs. The objective of this study was to evaluate the possible anxiolytic-simile effect of synthetic chalcone N-{(4'-[(E)-3-(4-fluorophenyl)-1-(phenyl) prop-2-en-1-one]} acetamide (PAAPFBA) on adult zebrafish (Danio rerio). PAAPFBA was synthesized with an 88.21% yield and its chemical structure was determined by 1H and 13C NMR. Initially, animals (n = 6/group) were treated (4 or 12 or 40 mg/kg, intraperitoneal) with PAAPFBA and were submitted to acute toxicity and open field tests. Then, other groups (n = 6/each) received PAAPFBA for the analysis of its effect on the Light & Dark Test. The participation of the GABAergic system was also assessed using the GABAA antagonist flumazenil. Molecular docking was performed using the GABAA receptor. The effect of PAAPFBA on anxiety induced by alcohol withdrawal was analyzed. PAAPFBA was non-toxic, reduced the locomotor activity, and showed an anxiolytic-like effect in both models. This effect was reduced by pre-treatment with the flumazenil. In agreement with in vivo studies, molecular docking indicated an interaction between chalcone and the GABAA receptor. The results suggest that PAAPFBA is an anxiolytic agent mediated via the GABAergic system.