Post-sensitization treatment with rimonabant blocks the expression of cocaine-induced behavioral sensitization and c-Fos protein in mice

Post-sensitization treatment with rimonabant blocks the expression of cocaine-induced behavioral sensitization and c-Fos protein in mice

Author Marinho, Eduardo A. V. Google Scholar
Oliveira-Lima, Alexandre J. Google Scholar
Yokoyama, Thais S. Autor UNIFESP Google Scholar
Santos-Baldaia, Renan Autor UNIFESP Google Scholar
Ribeiro, Luciana T. C. Autor UNIFESP Google Scholar
Baldaia, Marilia A. Autor UNIFESP Google Scholar
da Silva, Raphael Wuo Autor UNIFESP Google Scholar
Hollais, Andre Willian Autor UNIFESP Google Scholar
Talhati, Fernanda Autor UNIFESP Google Scholar
Longo, Beatriz Monteiro Autor UNIFESP Google Scholar
Berro, Lais Fernanda Autor UNIFESP Google Scholar
Frussa-Filho, Roberto Autor UNIFESP Google Scholar
Abstract CB1 receptor antagonists have been shown to prevent acute and long-term behavioral effects of cocaine. Here we evaluate the effectiveness of the CB1 receptor antagonist rimonabant to modify sensitized responses to cocaine. Mice were treated with saline or cocaine injections in a 15-day intermittent sensitization treatment and subsequently treated with either vehicle, 1 or 10 mg/kg rimonabant in the drug-associated environment for 8 consecutive days. Animals were then challenged with saline and cocaine in the open-field apparatus on subsequent days to evaluate the expression of conditioned and sensitized effects to cocaine. c-Fos protein expression was evaluated in the nucleus accumbens (NAcc), ventral tegmental area (VTA), basolateral amygdala (BLA), medial prefrontal cortex (mPFC) and caudate-putamen (CPu) after the last (cocaine) challenge. Previous treatment with 10 mg/kg rimonabant blocked the expression of conditioned hyperlocomotion and behavioral sensitization to cocaine, but not acute cocaine-induced hyperlocomotion. These behavioral effects were accompanied by significant changes in c-Fos expression in the brain reward system. Chronic cocaine sensitization blunted a subsequent acute cocaine-induced increase in c-Fos protein in the NAcc, effect that was reversed by previous treatment with rimonabant. Treatment with 10 mg/kg rimonabant also attenuated the significant increase in c-Fos expression in the CPu, mPFC and BLA induced by previous chronic sensitization with cocaine. Our findings add to the evidence that drugs targeting CB1 receptors are good candidates for the treatment of cocaine abuse and provide further insights into the mechanisms underlying endocannabinoid signaling within the brain reward system in the context of cocaine abuse.
Keywords Behavioral sensitization
C-Fos expression
xmlui.dri2xhtml.METS-1.0.item-coverage Oxford
Language English
Sponsor Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
Associacao Fundo de Incentivo a Pesquisa (AFIP)
Date 2017
Published in Pharmacology Biochemistry And Behavior. Oxford, v. 156, p. 16-23, 2017.
ISSN 0091-3057 (Sherpa/Romeo, impact factor)
Publisher Pergamon-Elsevier Science Ltd
Extent 16-23
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000401380500003

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