Antidepressant effect of aminophylline after ethanol exposure

Abstract

This work investigated the association of acute ethanol and aminophylline administration on behavioral models of depression and prefrontal monoamine levels (i.e. norepinephrine and dopamine) in mice. The animals received a single dose of ethanol (2 g/kg) or aminophylline (5 or 10 mg/kg) alone or in association. Thirty minutes after the last drug administration, the animals were assessed in behavioral models by the forced swimming and tail suspension tests. After these tests, the animals were sacrificed and the prefrontal cortices dissected to measure monoamine content. Results showed that ethanol presented depression-like activity in the forced swimming and tail suspension tests. These effects were reversed by the association with aminophylline in all tests. Norepinephrine and dopamine levels decreased, while an increase in the dopamine metabolite, (4-hydroxy-3-methoxyphenyl)acetic acid (DOPAC), after ethanol administration was observed. On the contrary, the association of ethanol and aminophylline increased the norepinephrine and dopamine content, while it decreased DOPAC when compared to the ethanol group, confirming the alterations observed in the behavioral tests. These data reinforce the involvement of the adenosinergic system on ethanol effects, highlighting the importance of the norepinephrine and dopamine pathways in the prefrontal cortex to the effects of ethanol.

Keywords: Adenosine; Aminophylline; Behavior; Ethanol; Monoamines; Prefrontal cortex.

Fig. 1

Evaluation of the potential antidepressant-like activity of the association of ethanol and aminophylline using the forced swimming test. Animals were preconditioned 24h before the test, being exposed for 15 min in a water tank, without drugs. On the test day, 30 minutes after the drug administration, animals were tested in the forced swimming test, with the immobility time as the parameter observed over 5 minutes. a, b, c, d mean statistically significant differences, as related to the Control, E, A5, and A10 groups, respectively. p<0.05 (ANOVA followed by Tukey as the post hoc test). (Abbreviations: E: ethanol, A: aminophylline).

Fig. 2

Evaluation of the potential antidepressant activity of the association of ethanol and aminophylline using the tail suspension test. Thirty minutes after the drug administration, the animals were tested in the tail suspension test, with the immobility time as the parameter observed over 6 minutes. a, b mean statistically significant differences, as related to the Control and E groups, respectively. p<0.05 (ANOVA followed by Tukey as the post hoc test). (Abbreviations: E: ethanol, A: aminophylline).

Fig. 3

Effects of ethanol associated with aminophylline on monoamine levels in mice prefrontal cortices. Data are presented as the mean ± S.E.M. (n = 4–14). a, b, c, d, and e mean statistically significant differences with p < 0.05 as compared to the controls, A5, A10, and E/A5 groups, respectively. NE, norepinephrine; DA, dopamine; DOPAC, 4-hydroxy-3-methoxy-phenylacetic acid.