Neuroadaptations and behavioral alterations related to ethanol addiction: effects of N-acetylcysteine treatment in mice

• Grant number: 14/02371-9
• Support Opportunities: Regular Research Grants
• Duration: July 01, 2014 - June 30, 2016
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Marcelo Tadeu Marin
• Grantee: Marcelo Tadeu Marin
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated researchers: Cleopatra da Silva Planeta

Abstract

Ethanol addiction is a serious public health problem and current treatments for this syndrome are generally ineffective. Then new drugs are needed for this purpose. N-acetylcysteine (N-Ac) has shown efficacy in the treatment of cocaine and nicotine addiction and in pre-clinical research and pilot clinical trials. However, there is no data on the possible application of N-Ac on ethanol addiction. Drug addiction is related to the development of neuroadaptations in neural circuits that mediate the reinforcing properties of these drugs. These neuroadaptations may involve several proteins, such as the transcription factor CREB, which is altered after chronic ethanol or other abuse drugs administration and are correlated to addiction behaviors. Furthermore, ”FosB is a protein that accumulates in the neurons after its repeated activation and mediates long lasting changes in response to abuse drugs. These changes are expressed mainly in neurons in the nucleus accumbens and amygdala. The aims of this project are evaluate the effects of treatment with N-Ac in behaviors related to ethanol addiction and the neuroadaptations produced by the administration of this abuse substance. For this purpose it will be evaluated possible changes in mice caused by administration of N-Ac in the following behaviors related to ethanol addiction: a) intake, b) intake inflexibility, c) conditioned place preference, and d) induction and expression of behavioral sensitization. In addition, it will also be investigated ethanol-induced neuroadaptations and its possible inhibition by N-Ac counting the positive neurons for ”FosB and active CREB (phosphorylated CREB ) by immunohistochemistry in the nucleus accumbens and amygdala. (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)

MORAIS-SILVA, GESSYNGER; ALVES, GABRIELLE CUNHA; MARIN, MARCELO T.. N-acetylcysteine treatment blocks the development of ethanol-induced behavioural sensitization and related Delta FosB alterations. Neuropharmacology, v. 110, n. A, p. 135-142, NOV 2016. (14/02371-9, 15/01026-9)

MORAIS-SILVA, GESSYNGER; ALVES, GABRIELLE CUNHA; MARIN, MARCELO T.. N-acetylcysteine treatment blocks the development of ethanol-induced behavioural sensitization and related Delta FosB alterations. Neuropharmacology, v. 110, p. 8-pg., 2016-11-01. (15/01026-9, 14/02371-9)

LAVERDE, CELINA FERRARI; MORAIS-SILVA, GESSYNGER; SANTANA AMARAL, VANESSA CRISTIANE; MARIN, MARCELO TADEU. Effects of N-acetylcysteine treatment on ethanol's rewarding properties and dopaminergic alterations in mesocorticolimbic and nigrostriatal pathways. Behavioural Pharmacology, v. 32, n. 2-3, p. 239-250, APR 2021. (14/02371-9)