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PKM participation on the contextual influence in locomotor sensitization induced by anfetamine

Grant number: 09/16305-0
Support Opportunities:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): June 01, 2010
Effective date (End): October 31, 2014
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Luiz Eugenio Araujo de Moraes Mello
Grantee:Douglas Senna Engelke
Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil


Drug addiction seems to be a process of usurpation of the physiological mechanisms of learning and memory due to intense plasticity in cortical and limbic circuits recruited during the drug seeking behavior. Animal models of drug addiction are very important to understand the neural basis of this illness that comprises several mechanisms of neural adaptations. Locomotor sensitization has been extensively used to investigate incentive salience and the transition from use to abuse. Furthermore, there are several studies reporting the influence of contextual aspects in the acquisition and expression of locomotor sensitization. However, these studies do not explore whether its maintenance is context specific. The maintenance of memories is a highly complex process involving many molecular mechanisms. However, recent findings suggest that the protein kinase M Zeta (PKMζ) is necessary and sufficient for this role. Although little is known about the neurochemical mechanisms involved in the action of PKMζ, it is known that this kinase upregulate AMPA receptor type 2 (GluR2) expression, and, consequently, promotes intense plasticity in cortical and limbic regions. Therefore, we believe that there is a relationship of protein PKMζ with addiction to amphetamine. To address this question, we will study (1) how long lasting and context-dependent is locomotor sensitization induced by amphetamine; (2) the expression of PKMζ in the hippocampus, nucleus accumbens and frontal cortex. Our experimental hypothesis is that there will be a contextual relationship with the locomotor sensitization and the expression of PKMζ will be associated with this memory. To study the PKMζ expression in the main structures related with addiction will enable a better understanding of the dynamics of the mesolimbic pathway might bringing up an important target for prevention and treatment of drug addiction. (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)
ENGELKE, DOUGLAS SENNA; FILEV, RENATO; MELLO, LUIZ E.; SANTOS-JUNIOR, JAIR GUILHERME. Evidence of memory generalization in contextual locomotor sensitization induced by amphetamine. Behavioural Brain Research, v. 317, p. 522-527, . (09/16305-0, 09/16307-2)
TORTORELLI, LUCAS SILVA; ENGELKE, DOUGLAS SENNA; LUNARDI, PAULA; MELLO E SOUZA, TADEU; SANTOS-JUNIOR, JAIR GUILHERME; GONCALVES, CARLOS-ALBERTO. Cocaine counteracts LPS-induced hypolocomotion and triggers locomotor sensitization expression. Behavioural Brain Research, v. 287, p. 226-229, . (09/16305-0)
COELHOSO, CASSIA C.; ENGELKE, DOUGLAS S.; FILEV, RENATO; SILVEIRA, DARTIU X.; MELLO, LUIZ E.; SANTOS-JUNIOR, JAIR G.. Temporal and Behavioral Variability in Cannabinoid Receptor Expression in Outbred Mice Submitted to Ethanol-Induced Locomotor Sensitization Paradigm. ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH, v. 37, n. 9, p. 1516-1526, . (09/16305-0, 09/16307-2, 11/03184-0)

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