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Cross-sensitization between stress and amphetamine: pre and post sinaptic neuroadaptation in mesocorticolimbic system

Grant number: 07/08087-7
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): June 01, 2008
Effective date (End): May 31, 2011
Field of knowledge:Biological Sciences - Pharmacology - Neuropsychopharmacology
Principal Investigator:Cleopatra da Silva Planeta
Grantee:Fabio Cardoso Cruz
Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil


Repeated stress exposure engenders behavioral sensitization to psychostimulant drugs and may also increase the potential for abuse of psychomotor stimulants. Psychostimulants and stress activate extracellular signal-regulated kinase (ERK) and CREB in the mesolimbic dopaminergic circuit. These molecular pathway are essential components of a signaling process involved in synaptic plasticity and long-term effects of drugs of abuse. In addition it has been demonstrated that repeated stress or psychostimulant exposure increases dopamine levels in mesocorticolimbic system. However alterations in these parameters in the interaction between drug and stress have been poorly investigated. The present study will examine the relationship between stress – induced behavioral sensitization and changes in ERK, CREB e dopamine levels in nucleus accumbens, pre-frontal cortex, ventral tegmental area and amigdala in adult and adolescent rats. Adolescent and adult Wistar male rats will be subjected to two hours of immobilization stress for 10 days. Three days after the last stress session the behavioral response to an amphetamine challenge will be evaluated. Immediately follwing the behavioral analysis, rats will be decapitated and the encefalic structure will be dissected to determine dopamine and metabolites levels by HPLC and phosphorilated ERK and CREB and dopamine transporter by western blot. (AU)

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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)
CRUZ, FABIO C.; MARIN, MARCELO TADEU; LEAO, RODRIGO MOLINI; PLANETA, CLEOPATRA S.. Stress-induced cross-sensitization to amphetamine is related to changes in the dopaminergic system. JOURNAL OF NEURAL TRANSMISSION, v. 119, n. 4, p. 415-424, . (07/08087-7)
CARNEIRO DE OLIVEIRA, PAULO E.; LEAO, RODRIGO M.; BIANCHI, PAULA C.; MARIN, MARCELO T.; PLANETA, CLEOPATRA DA SILVA; CRUZ, FABIO C.. Stress-Induced Locomotor Sensitization to Amphetamine in Adult, but not in Adolescent Rats, Is Associated with Increased Expression of Delta FosB in the Nucleus Accumbens. FRONTIERS IN BEHAVIORAL NEUROSCIENCE, v. 10, . (07/08087-7)

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