Paula Cristina Bianchi1, Paulo Eduardo Carneiro de Oliveira2, Paola Palombo1, Rodrigo Molini Leão3, Hugo Cogo-Moreira4, Cleopatra da Silva Planeta1, Fábio Cardoso Cruz5. 1. Laboratory of Pharmacology, São Paulo State University, Rod. Araraquara-Jaú km 1, 14801-902, Araraquara-SP, Brazil; Joint Graduate Program in Physiological Sciences, Federal University of São Carlos and São Paulo State University Araraquara, Rod. Washington Luís km 235, 13565-905, São Carlos-SP, Brazil. 2. Laboratory of Pharmacology, São Paulo State University, Rod. Araraquara-Jaú km 1, 14801-902, Araraquara-SP, Brazil. 3. Bioregulation Department Federal University of Bahia, UFBA, Av. Reitor Miguel Calmon s/n Vale do Canela Salvador/BA, Brazil. 4. Department of Psychiatry, São Paulo Federal University, R. Dr. Ovidio Pires de Campos, 78505403-903, SP, Brazil. 5. Department of Pharmacology, São Paulo Federal University, Leal Prado Building, Botucatu 862 Street, 04024-002, Vila Clementino, São Paulo-SP, Brazil. Electronic address: f.cruz@unifesp.br.
Abstract
BACKGROUND: The high rate of relapse to drug use remains a central challenge to treating drug addiction. In human and rat models of addiction, environmental stimuli in contexts associated with previous drug use can provoke a relapse of drug seeking. Pre-clinical studies have used the ABA renewal procedure to study context-induced reinstatement of drug seeking. In the current study, we studied the role of the orbitofrontal cortex (OFC) in context-induced reinstatement to alcohol. METHODS: We trained male and female rats to self-administer alcohol in context A, extinguished drug-reinforced responding in a distinct context B, and assessed context-induced reinstatement in context A or B (control group). Next, we determined the effect of context-induced renewal of alcohol-seeking behavior on the expression of Fos (a neuronal activity marker) in the OFC. Finally, we determined the effect of reversible inactivation by GABAa and GABAb receptor agonists (i.e., muscimol and baclofen, respectively) in the OFC. RESULTS AND CONCLUSIONS: There were no differences between male and female rats in context-induced reinstatement of alcohol-seeking behavior. Re-exposure to Context A, but not Context B, reinstated alcohol-seeking behavior and increased expression of the neural activity marker Fos in the OFC. Reversible inactivation of the OFC with muscimol and baclofen attenuated context-induced reinstatement. Our data indicated that the OFC mediates context-induced reinstatement of alcohol-seeking behavior.
BACKGROUND: The high rate of relapse to drug use remains a central challenge to treating drug addiction. In human and rat models of addiction, environmental stimuli in contexts associated with previous drug use can provoke a relapse of drug seeking. Pre-clinical studies have used the ABA renewal procedure to study context-induced reinstatement of drug seeking. In the current study, we studied the role of the orbitofrontal cortex (OFC) in context-induced reinstatement to alcohol. METHODS: We trained male and female rats to self-administer alcohol in context A, extinguished drug-reinforced responding in a distinct context B, and assessed context-induced reinstatement in context A or B (control group). Next, we determined the effect of context-induced renewal of alcohol-seeking behavior on the expression of Fos (a neuronal activity marker) in the OFC. Finally, we determined the effect of reversible inactivation by GABAa and GABAb receptor agonists (i.e., muscimol and baclofen, respectively) in the OFC. RESULTS AND CONCLUSIONS: There were no differences between male and female rats in context-induced reinstatement of alcohol-seeking behavior. Re-exposure to Context A, but not Context B, reinstated alcohol-seeking behavior and increased expression of the neural activity marker Fos in the OFC. Reversible inactivation of the OFC with muscimol and baclofen attenuated context-induced reinstatement. Our data indicated that the OFC mediates context-induced reinstatement of alcohol-seeking behavior.
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Authors: Paula C Bianchi; Lucas Gomes-de-Souza; Willian Costa-Ferreira; Paola Palombo; Paulo E Carneiro de Oliveira; Sheila A Engi; Rodrigo M Leão; Cleopatra S Planeta; Carlos C Crestani; Fabio C Cruz Journal: Biol Sex Differ Date: 2021-03-16 Impact factor: 5.027