Involvement of Pre-limbic Cortex-Nucleus accumbens projections in Context-Induced alcohol seeking

Autor(es)

Bianchi, Paula Cristina ; Palombo, Paola ; Engi, Sheila Antonagi ; de Oliveira, Paulo Eduardo Carneiro ; Tavares, Gabrielle Emily Boaventura ; Anjos-Santos, Alexia ; Yokoyama, Thais Suemi ; Planeta, Cleopatra da Silva ; Cruz, Fabio Cardoso ; Leao, Rodrigo Molini

• Tipo de documento: Artigo Científico
• Fonte: Brain Research; v. 1841, p. 16-pg., 2024-06-15.

Resumo

Alcohol use disorder (AUD) remains a critical public health issue worldwide, characterized by high relapse rates often triggered by contextual cues. This research investigates the neural mechanisms behind context-induced reinstatement of alcohol-seeking behavior, focusing on the nucleus accumbens and its interactions with the prelimbic cortex, employing Male Long -Evans rats in an ABA renewal model. In our experimental setup, rats were trained to self-administer 10 % ethanol in Context A, followed by extinction of lever pressing in the presence of discrete cues in Context B. The context-induced reinstatement of ethanol-seeking was then assessed by re-exposing rats to Context A or B under extinction conditions, aiming to simulate the environmental cues ' influence on relapse behaviors. Three experiments were conducted: Experiment 1 utilized Fosimmunohistochemistry to examine neuronal activation in the nucleus accumbens; Experiment 2 applied the baclofen + muscimol inactivation technique to probe the functional importance of the nucleus accumbens core; Experiment 3 used Fos-immunofluorescence along with Retrobeads injection to investigate activation of neurons projecting from the prelimbic cortex to the nucleus accumbens core. Our findings revealed significant increases in Fos-immunoreactive nuclei within the nucleus accumbens core and shell during the reinstatement phase in Context A, underscoring the environment 's potent effect on ethanol-seeking behavior. Additionally, inactivation of the nucleus accumbens core markedly reduced reinstatement, and there was a notable activation of neurons from the prelimbic cortex to the nucleus accumbens core in the ethanol-associated context. These results highlight the critical role of the nucleus accumbens core and its corticostriatal projections in the neural circuitry underlying context -driven ethanol seeking. (AU)

• Processo FAPESP: 14/02296-7 - Manipulação Farmacogenética e Investigação de Alterações Moleculares em Sinapses entre Neurônios Seletivamente Ativados na Reinstalação da Autoadministração de Etanol
• Beneficiário: Rodrigo Molini Leão
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 13/24986-2 - Participação de pequenos grupos neurais seletivamente ativados (neuronal ensembles) na reinstalação da autoadministração de etanol induzida pelo ambiente: investigação farmacogenética, optogenética e molecular
• Beneficiário: Fabio Cardoso Cruz
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 18/15505-4 - Estudo neurobiológico da recaída ao uso de cocaína e crack: identificação de plasticidades em neuronal ensembles que armazenam memórias relacionadas com a adição de drogas
• Beneficiário: Fabio Cardoso Cruz
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores - Fase 2