Antidepressant Effect of Aminophylline After Ethanol Exposure

Sarah Souza Escudeiro

doi:10.3797/scipharm.1208-17

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.

Highlights

Ethanol differentially interferes with the transmission processes in the central nervous system, affecting neurotransmitters [1, 2] and leading to a variety of behavioral and physiological changes such as motor incoordination, memory impairment, anxiety reduction, and depression, among others [3,4,5]
Among the wide range of pathways in the central nervous system that are modified by ethanol, it is important to highlight those that underlie ethanol’s diverse effects, like the ones related to the release of gamma-amynobutiric acid (GABA), glutamate, dopamine, and norepinephrine [11, 12]
Because ethanol causes depression-like behavior, the present study investigated the ability of aminophylline, a non-selective adenosine receptor antagonist, to reverse ethanol’s behavioral alteration using the tail suspension and forced swimming tests

Summary

Introduction

Ethanol differentially interferes with the transmission processes in the central nervous system, affecting neurotransmitters [1, 2] and leading to a variety of behavioral and physiological changes such as motor incoordination, memory impairment, anxiety reduction, and depression, among others [3,4,5]. Among the wide range of pathways in the central nervous system that are modified by ethanol, it is important to highlight those that underlie ethanol’s diverse effects, like the ones related to the release of gamma-amynobutiric acid (GABA), glutamate, dopamine, and norepinephrine [11, 12]. Another pathway that is of increasing interest in research about ethanol’s effects is the adenosine system [13,14,15]. Clinical and experimental evidence showed that reduced adenosinergic activity is involved in bipolar mania and aggressive behavior [21] and A2A receptors have been implicated in panic disorders [22]

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Results

Conclusion