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Stress and nicotine self-administration: involvement of CREB, PKA and ERK transduction pathway in the nucleus accumbens and pre-frontal cortex

Grant number: 08/10691-2
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): March 01, 2009
Effective date (End): March 31, 2013
Field of knowledge:Biological Sciences - Pharmacology - Neuropsychopharmacology
Principal Investigator:Cleopatra da Silva Planeta
Grantee:Rodrigo Molini Leão
Home Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil


About 5 million people die each year due to diseases related to tobacco smoking (WHO, 2002). Evidence suggests that nicotine, which acts at neuronal nicotinic acetylcholine receptors, is one of the active components in tobacco smoke responsible for tobacco addiction. Intravenous drug self-administration in rodents is a useful procedure for predicting the abuse liability of drugs in humans and for studying the biological basis of addiction. Drug addiction is considered a neuroadaptative disorder characterized by neurochemical and molecular changes following drug exposure. Several clinical and pre-clinical researches suggest that the exposure to stress is correlated with compulsive drug abuse. Although stress is clearly considered a risk factor for nicotine abuse and addiction few studies evaluate how exposure to stress could affect nicotine self - administration in animal models. In addition, the molecular mechanisms involved in stress - induced increased vulnerability to nicotine abuse and addiction has not been elucidated yet. The aim of the present project is to investigate: a) whether exposure to chronic variable stress increases nicotine self - administration; b) ERK, CREB, PKA activity, in the nucleus accumbens and pre-frontal cortex in response to nicotine challenge, following the exposure to variable stress; c) whether the neuroadaptations induced by stress are long-lasting or they can be change for nicotine self-administration procedure. We hypothesized that stress increases nicotine break point and binge, which could be associated with adaptations in dopamine transmission that can be evaluated by ERK, CREB and PKA activity in the nucleus accumbens and pre-frontal cortex. (AU)

News published in Agência FAPESP Newsletter about the scholarship:
Brazilian neuroscientists examine relapse among drug users 

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)
LEAO, RODRIGO M.; CRUZ, FABIO C.; CARNEIRO-DE-OLIVEIRA, PAULO E.; ROSSETTO, DANIELLA B.; VALENTINI, SANDRO R.; ZANELLI, CLESLEI F.; PLANETA, CLEOPATRA S. Enhanced nicotine-seeking behavior following pre-exposure to repeated cocaine is accompanied by changes in BDNF in the nucleus accumbens of rats. Pharmacology Biochemistry and Behavior, v. 104, p. 169-176, MAR 2013. Web of Science Citations: 7.
LEAO, RODRIGO MOLINI; CRUZ, FABIO CARDOSO; MARIN, MARCELO TADEU; PLANETA, CLEOPATRA DA SILVA. Stress induces behavioral sensitization, increases nicotine-seeking behavior and leads to a decrease of CREB in the nucleus accumbens. Pharmacology Biochemistry and Behavior, v. 101, n. 3, p. 434-442, MAY 2012. Web of Science Citations: 12.

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