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EFEITOS AGUDOS DA ASSOCIAÇÃO DE ETANOL E MINOFILINA EM TESTES COMPORTAMENTAIS E NEUROQUÍMICOS EM CAMUNDONGOS / ACUTE EFFECTS OF THE ASSOCIATION OF ETHANOL ON TESTING AND AMINOPHYLLINE BEHAVIORAL AND NEUROCHEMICAL IN MICE
Sarah de Souza Escudeiro
DATA DE PUBLICAÇÃO
Ethanol effects in central nervous system (CNS) are due to its action in several neurotransmitter systems, changing the existing balance in inhibitory and excitatory pathways. Aminophylline, a methylxanthine with stimulant action, is an adenosine receptor antagonist, and actually used in treatment of asthma and consciousness recovery after long period of anesthesia. Several studies have investigated the interaction between adenosine pathway and the depressant effects of ethanol. This study investigated the acute effects of the interaction of ethanol and aminophylline in behavioral and neurochemical test in mice. Swiss male mice, weighing 25-30 g were used. Aminals were treated with distiled water (control), ethanol (p.o.) or aminophylline (i.p.). Another group was pretreated with ethanol (2 g/kg) 30 min prior to aminophylline (5 or 10 mg/kg) administration. Thirty minutes after aminophylline administration or 60 minutes after ethanol administration, animals were tested in open field (locomotor activity), tail suspension and forced swimming (antidepressant activity) apparatus. After the tests animals were sacrificed and the brains dissected. Pre-frontal cortex (CPF) was used to determine monoamine and its metabolites concentration (NE, DA, DOPAC). To evaluate the neuroprotective effect of the drugs studied, animals were dissected and CPF, hippocampus (HC) and striatum (CE) homogenized with phosphate buffer to determine TBARS and catalase activity. In the present study, ethanol showed a depressant effect, as indicated by the reduction in squares crossed and rearing in open field test, and the increase in the immobility time in both testes to evaluate antidepressant activity. On the other hand, aminophylline showed a stimulant effect, presenting opposite features in almost all parameters observed in groups treated with ethanol. Indeed, depressive effect induced by ethanol was followed by a reduction in NE and DA concentrations in CPF, being this effect reversed by the association group. Ethanol promoted oxidative stress, rising lipid peroxidation and catalase activity. On the other hand, aminophylline showed a neuroprotective effect, reducing these parameters when administered after ethanol in all three areas tested. Aminophylline administration after ethanol treatment is able to block the reduction in exploratory and depressant activities induced by ethanol, probably acting through noradrenergic and dopaminergic pathways in CPF, beyond reduce the oxidative stress induced by ethanol, suggesting a new target for the blockade of ethanol depressant and oxidant effects.