masterThesis
Agomelatina em ratas: efeitos sobre comportamentos relacionados à ansiedade à luz do seu efeito antidepressivo
Fecha
2019-02-28Registro en:
GOMES, Ana Clara da Costa Nunes. Agomelatina em ratas: efeitos sobre comportamentos relacionados à ansiedade à luz do seu efeito antidepressivo. 2019. 72f. Dissertação (Mestrado em Ciências Biológicas) - Centro de Biociências, Universidade Federal do Rio Grande do Norte, Natal, 2019.
Autor
Gomes, Ana Clara da Costa Nunes
Resumen
Agomelatine is a MT1 and MT2 receptors agonist and 5-HT2C receptor
antagonist used in the pharmacotherapy of depressive disorders. In
addition, its use has been suggested to relieve symptoms of anxiety
disorders, including panic attacks. The aim of present study was to evaluate
if agomelatine administration alters anxiety and panic-related responses in
female rats. Wistar rats were submitted to two tests of anxiety based on
innate aversion of rodent to open and unprotected places, the elevated plusmaze (EPM), the elevated T-maze (ETM) and to the open field test (OF),
the latter to evaluate indices of anxiety and the locomotor activity of the rats.
In our results, twe observed that there were no changes in the locomotor
activity of the females submitted to the oral administration of agomelatine in
short term (25, 50 or 75 mg/kg, 60 minutes before the test), as assessed in
the open field test and EPM. Regarding anxiety-like responses, the
administration of agomelatine (12.5, 25 or 50 mg/kg, 60 minutes before the
test) did not alter the exploration of the EPM. In ETM, agomelatine
administred sixty minutes before the pre-test and test sessions did not
modify the inhibitory avoidance acquisition or escape response at doses of
50 and 75 mg/kg. However, the dose of 25 mg/kg favored a reduction in
latency to the escape, suggesting a panicogenic-like effect. In the absence
of efficacy of short-term administration of agomelatine on experimental
anxiety, and in order to confirm its antidepressive efficacy in females, the
rats submitted to ETM have been submitted to administration of the same
doses of agomelatine previous 60 minutes to OF, pretest and forced
swimming test (FST), with a 24-hour interval between procedures. In FST,
administration of agomelatine (50 and 75 mg/kg) did not alter climbing
behavior, but reduced immobility time, thus reinforcing in females the
antidepressant-like profile of this drug. Thus, in order to verify whether longterm administration of agomelatine would favor an anxiolytic and/or
panicolytic effect, an independent rat group was administered for 25 days
agomelatine at a dose of 50 mg/kg and, 60 minutes after the last
administration, to the ETM, OF and blood test for biochemical (AST and
ALT) and histological analysis of the liver. The long-term administration of
agomelatine did not change any of the parameters analyzed, suggesting the
absence of behavioral effects and hepatotoxicity. The data obtained here
show a lack of anxiolytic profile of agomelatine in short and long term, but
confirm their antidepressant potential in the short term in females.