Stress and nicotine self-administration: involvement of CREB, PKA, and ERK transduction pathway in the dopamine mesocorticlimbimc system

• Grant number: 08/01744-5
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2008
• End date: June 30, 2010
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Cleopatra da Silva Planeta
• Grantee: Cleopatra da Silva Planeta
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

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 and relapse. Although stress is clearly considered a risk fact 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, and levels of dopamine and its metabolites in the dopamine mesolimbic system in response to a nicotine challenge, following the exposure to variable stress. We hypothesized that stress increases nicotine break point and binge, which could be associated with adaptations in the dopamine transmission that might be measured by changes dopamine levels and ERK, CREB and PKA activity. (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)

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. (08/10691-2, 08/01744-5)

ZANCHETA, ROBERTA; POSSI, ANA P. M.; PLANETA, CLEOPATRA S.; MARIN, MARCELO T.. Repeated administration of caffeine induces either sensitization or tolerance of locomotor stimulation depending on the environmental context. PHARMACOLOGICAL REPORTS, v. 64, n. 1, p. 70-77, JAN-FEB 2012. (08/01744-5)