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Neurobiology study of relapse to alcohol and cocaine seeking: identification of plasticity in neuronal ensembles that encodes addiction-related memories

Grant number: 18/15505-4
Support Opportunities:Research Grants - Young Investigators Grants - Phase 2
Duration: May 01, 2019 - April 30, 2025
Field of knowledge:Biological Sciences - Pharmacology - Neuropsychopharmacology
Principal Investigator:Fabio Cardoso Cruz
Grantee:Fabio Cardoso Cruz
Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Associated researchers:Cleopatra da Silva Planeta ; Gustavo José da Silva Pereira ; Paola Palombo ; Paula Cristina Bianchi ; Rodrigo Molini Leão ; Sheila Antonagi Engi
Associated research grant:13/24986-2 - The role of neuronal ensembles in context-induced reinstatement of ethanol seeking: pharmacogenetic, optogenetic and molecular investigation, AP.JP
Associated grant(s):19/23454-3 - The role of matricellular protein hevin in cocaine reward effects in mice, AV.EXT
Associated scholarship(s):23/14542-1 - Prenatal Exposure to Cocaine: Impacts on Neuronal Plasticity and Behavioral Sensitivity in Adolescent Rats, BP.IC
22/09953-0 - Transcriptome analysis of the bed nucleus of the stria terminalis (BNST) of mice subjected to the rat exposition stress-induced reinstatement of ethanol seeking, BP.MS
+ associated scholarships 22/02379-6 - Involvement of endocannabinoid system on locomotor cross-sensitization between social isolament stress and cocaine in adolescent mice, BP.IC
20/04389-3 - Maternal separation stress and behaviors related to alcohol dependence in mice: assessment of CRFergic neurotransmission, BP.DR
21/00838-0 - Investigation of the participation of hippocampal projections to infralimbic cortex and nucleus acumbens in the context-induced reinstatement of ethanol seeking, BP.DR
21/05094-0 - Mechanisms of behavioral inhibition: the neurophysiology of neuronal ensembles related to ethanol addiction, BP.PD
20/01331-4 - Effect of epigenetic changes in the nociceptin system caused by maternal separation stress on the consumption of ethanol in mice, BP.IC
19/24073-3 - Role of cannabinoid CB1 receptors in modulating neural circuits involved in the interaction between maternal separation stress and ethanol intake in mice, BP.PD
19/26246-2 - The role of differents subtypes of GABAergics interneurons on impulsive behavior and ethanol-seeking, BP.DR
20/01343-2 - Involvement of medial prefrontal cortex neuronal ensembles and its perineuronal NETs on incubation of cocaine craving, BP.IC
19/17065-4 - Neurobiology study of relapse to alcohol seeking: role of neuronal ensembles in the basolateral amygdala that encodes addiction-related memories, BP.PD
19/17799-8 - Neurobiology study of neuronal ensembles in the basolateral amygdala that encodes addiction-related memories, BP.MS
16/18701-3 - Cannabidiol treatment in behaviours related to ethanol addiction: in vitro and in vivo studies, BP.PD - associated scholarships


Correlational data suggests that learned associations are encoded within sparsely distributed patterns of neurons called neuronal ensembles that are selectively activated during learned behaviors. Until recently it has been difficult to prove that neuronal ensembles mediate learned behaviors because both traditional pharmacological and lesion methods, and newer optogenetic and chemo genetic methods alter activity of neurons regardless of whether they were selectively activated or not activated during learned behaviors. Additionally, previous studies on synaptic and molecular alterations induced by learning did not distinguish between behaviorally activated and non-activated neurons. Based on these considerations, we propose to combine some methodologies, considered as state-of-art (overlap, optogenetic regulation, FACS, causal role experiments, c-Fos::teop-Cre and LacZ rats) to assess different aspects of ensemble-specific neuroadaptations in different brain areas in context-induced reinstatement of alcohol seeking and incubation of cocaine seeking. Understanding the role of these neuronal ensembles in behavior and the ways that repeated drug administration alters them will help us to understand how drugs of abuse produce the learned behaviors associated with addiction. Aim 1: Identification and characterization of neuronal ensembles activated during incubation of cocaine craving behavior. We will use the cfos-tetO-Cre transgenic rats, FACS followed by spectrophotometry, optogenetic and virus vectors to identify and show causal role to neuronal ensembles in nucleus accumbens that are repeatedly activated during tests for incubation of cocaine craving.Aim 2: Demonstrated context-specific selection of neuronal ensembles that were distinct when exposed to alcohol self-administration training context or extinction context. We intend to demonstrate context-specific induction of the pharmacogenetic (beta-galactosidase) and optogenetic protein (channel rhodopsin) in these neuronal ensembles that will be used to show selective inhibition of memories associated with alcohol taking or extinction of alcohol seeking. (AU)

Articles published in Pesquisa FAPESP Magazine about the research grant:
Una potencial vacuna contra la cocaína 
A potential vaccine against cocaine abuse 
Articles published in Agência FAPESP Newsletter about the research grant:
Articles published in other media outlets (0 total):
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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)
FERREIRA, SARA EMI M. M.; SOARES, LEONARDO M.; LIRA, CLARICE R.; YOKOYAMA, THAIS S.; ENGI, SHEILA A.; CRUZ, FABIO C.; LEA, RODRIGO M.. Ethanol-induced locomotor sensitization: Neuronal activation in the nucleus accumbens and medial prefrontal cortex. Neuroscience Letters, v. 749, . (18/15505-4)
FELIPE, JAQUELINE MOREIRA; PALOMBO, PAOLA; BIANCHI, PAULA CRISTINA; ZANIBONI, CAROLINE RIBERTI; ANESIO, AUGUSTO; YOKOYAMA, THAIS SUEMI; ENGI, SHEILA ANTONAGI; CARNEIRO-DE-OLIVEIRA, PAULO EDUARDO; PLANETA, CLEOPATRA DA SILVA; LEAO, RODRIGO MOLINI; et al. Dorsal hippocampus plays a causal role in context-induced reinstatement of alcohol-seeking in rats. Behavioural Brain Research, v. 398, . (18/15505-4)
FAVORETTO, C. A.; BERTAGNA, N. B.; RIGHI, T.; RODOLPHO, B. T.; ANJOS-SANTOS, A.; SILVA, F. B. R.; BIANCHI, P. C.; CRUZ, F. C.. Impacts of maternal separation stress on ethanol-related responses, anxiety-and depressive-like behaviors in adolescent mice. Neuroscience Letters, v. 809, p. 12-pg., . (19/24073-3, 18/15505-4)

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