Avaliação dos efeitos do complexo metálico derivado do diazepam [(DZP)PdCl]2 nos comportamentos relacionados com medo, ansiedade e memória em camundongos swiss

Abstract

The challenge in the therapy of anxiety disorders is to identify effective alternative medicines with better tolerability. Some studies have shown that the synthesis and semi-synthesis of metal compounds derived from benzodiazepines (BDZs) exhibit these desirable characteristics of the novel anxiolytic drugs. Based on that, the objective of this work was to evaluate the effects of intraperitoneal (i.p.) administration of metal complex derived from diazepam [(DZP)PdCl]2 on fear, anxiety and memory related behaviors in female Swiss mice. For this, female Swiss mice were treated (i.p.) with the preparation drug vehicle (Control group; NaCl 0,9%; Tween 80 0,5%) or [(DZP)PdCl]2 (0.015, 0.025 and 0.15 mg / kg). After 30 min of treatment, the animals were submitted to anxiety tests [elevated plus maze (EPM) or light-dark box (LDB)], locomotion [open field (OF)] and memory [step-down (SD)]. The role of the GABAA receptor in the anxiolytic-like effect of the [(DZP)PdCl]2 complex was evaluated after pretreatment with flumazenil (2 mg / kg, i.p) + [(DZP)PdCl]2 (best anxiolytic dose). In the LCE, [(DZP)PdCl]2 (0.15mg / kg) increased significantly the %TBA and %EBA, when compared to the control group, indicating an anxiolytic-like behavior. The effect of the anxiolytic-like was not observed in the LDB. No locomotor change was found in the OF test, as well as no amnesic change SD. Flumazenil per se did not alter any of the parameters evaluated in the EPM, but was able to block the anxiolytic-like effect of [(DZP)PdCl]2, indicating that this anxiolytic-like effect occurs by way of the BDZ site in the GABAA receptor complex. Our results demonstrated for the first time that [(DZP)PdCl]2 presents an anxiolytic-like effect in EPM and this effect is not influenced by locomotor activity nor does it promote amnesic effect. In addition, the anxiolytic type effect of the compound [(DZP)PdCl]2 is mediated by activation of the GABAA receptor. Further studies should be performed to evaluate the safety of compound [(DZP)PdCl]2.