Associação entre propensão ao alto consumo de etanol, comportamentos relacionados à dependência e alterações neurais: uma comparação entre camundongos C57BL/6J e Suíços

Abstract

Ethanol is the addictive drug most consumed worldwide and its misuse is a major factor contributing to the decline in global health. The severity of ethanol addiction as a public health problem, and its many consequences in an individual\'s social life and health, boost the importance of research on the neural mechanisms that contribute to this pathology. Information about the involvement of certain neurotransmitters and brain regions that are activated by ethanol are important in understanding the mechanisms involved in addiction. The aim of this work was to evaluate the association between propensity to high ethanol consumption and the development of addiction-related behaviors, also the relationship of brain monoamines and activation of neural areas with these behaviors. Male mice of Swiss and C57BL/6J (C57) strains were used, undergoing the following tests: (1) two bottle choice ethanol preference test, (2) inflexibility of ethanol consumption with the addition of quinine, (3) conditioned place preference (CPP) with ethanol as a conditioning agent, (4) quantification of locomotor activity, (5) evaluation of neuronal activation by expression of Fos protein and (6) quantification of the contents of noradrenaline (Nor), dopamine (DA) and serotonin (5-HT). Tests 3 to 6 were carried out after intraperitoneal injections of ethanol. C57 mice drank more ethanol than the Swiss ones, and also preferred the ethanol solution over tap water. One of the criteria for addiction diagnosis is drug use despite knowledge of its adverse consequences. The consumption and preference for ethanol solution of the Swiss strain was not reduced by the addition of quinine, while in the C57 strain this was a significant reduction. The CPP test revealed that only the Swiss animals were conditioned by ethanol, staying longer in an environment that was paired to the drug. Our results for the locomotion assays showed that both Swiss and C57 mice exhibited increased locomotor activity after ethanol injections than after saline injections, indicating that both strains are responsive to the psychomotor stimulant effects of the drug. The neuronal activation test showed that, overall, the Swiss are more responsive to ethanol, showing a greater number of activated regions after drug administration, while C57 showed a tendency to decrease activation in some regions related to ethanol consumption. The neurochemical results do not shown an increase in DA, 5-HT or Nor concentrations after ethanol administration, but in general the Swiss have higher basal concentrations of these neurotransmitters than C57. In this way, the high consumption of ethanol is not necessarily associated to the expression of dependence-related behaviors. The expression of addiction-related behaviors in the Swiss animals may be associated to increased neural activation by ethanol of areas related to reinforcement in these animals, and the tissue concentration of DA and 5-HT may be involved.