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Analysis of the influence of genetic polymorphism associated with peptide receptors and family CRF and environmental stress in the development of alcohol dependence

Grant number: 13/01158-7
Support type:Regular Research Grants
Duration: February 01, 2014 - July 31, 2016
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Isabel Cristina Céspedes
Grantee:Isabel Cristina Céspedes
Home Institution: Instituto de Saúde e Sociedade (ISS). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil
Assoc. researchers:João Bosco Pesquero ; Maria Lucia Oliveira de Souza Formigoni


Drug addiction is a worldwide problem and often involving young people and adults, with alcohol being the drug most commonly used and associated with numerous health and social problems. However, not all people who drink alcohol become addicted. The transition from casual use to addiction is influenced by positive reinforcement (state of pleasure from use) and negative (relief of unpleasant symptoms such as situations of stress or depression or withdrawal symptoms). There is a knowledge gap about the factors responsible for this transition. Drug dependence occurs in a sequence of events: contact with a drug that may become increasingly common and is characterized by an uncontrolled search (compulsion), with loss of control eating. After a period of abstinence, relapses often occur frequently. After an initial period of euphoria, the effects of the drug can result from a negative emotional state characterized by dysphoria, anxiety and irritability in the absence of the substance, thus manifesting withdrawal syndrome. These events reflect neuroadaptation processes triggered by chronic use of the drug, including among them tolerance and sensitization. Several neurotransmitter systems are involved in this process. The binge alcohol has been strongly associated with changes in the neurotransmitter systems involved in reward processes (especially dopamine). There may be also a recruitment mechanisms involving negative reinforcement processes underlying the adaptations to stress, highlighting the increased activity of system CRFérgico. Understanding the genetic basis underlying changes in stress and reward systems can contribute to the understanding of the mechanisms involved in the negative reinforcement that leads to addiction to alcohol and other drugs. There are few studies on the genetic factors involved in the mechanisms of positive reinforcement, especially for genes associated with dopaminergic and serotonergic systems. However, there are a limited number of studies in humans on the influence of CRFérgico system and its association with environmental stressors in alcohol dependence. This study aims to study the association between the presence of polymorphisms in genes associated with peptides and CRF receptor family, the presence and perception of stressful life events and alcohol dependence. Will be part of the study 400 individuals, 200 people diagnosed as alcohol dependent (in life) and 200 non-dependent, paired with the first group in relation to sociodemographic variables (age, gender and ethnicity). Will analyze the presence of polymorphisms in genes associated with peptides and CRF receptor family (CRH, UCN I, Crf1 and CRF2), history of stressful life events through the Life Experiences Survey (LES), the experience of traumatic experiences through Questionnaire About Childhood Traumas (QUESI), the current condition of perceived stress by the Perceived Stress Scale (PSS-10) and what situations trigger drinking through the Inventory of Drinking Situations (ISB). (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
WSCIEKLICA, TATIANA; LE SUEUR-MALUF, LUCIANA; PREARO, LEANDRO; CONTE, RAFAEL; VIANA, MILENA DE BARROS; CESPEDES, ISABEL CRISTINA. Chronic intermittent ethanol administration differentially alters DeltaFosB immunoreactivity in cortical-limbic structures of rats with high and low alcohol preference. AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE, v. 45, n. 3, p. 264-275, MAY 4 2019. Web of Science Citations: 1.
CONTE, RAFAEL; LOBO LADD, FERNANDO VAGNER; BARBOSA LOBO LADD, ALINY ANTUNES; MOREIRA, AMANDA LOPEZ; LE SUEUR-MALUF, LUCIANA; VIANA, MILENA DE BARROS; CESPEDES, ISABEL CRISTINA. Behavioral and stereological analysis of the prefrontal cortex of rats submitted to chronic alcohol intake. Behavioural Brain Research, v. 362, p. 21-27, APR 19 2019. Web of Science Citations: 4.

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