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

Author(s)

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

• Document type: Journal article
• Source: Brain Research; v. 1841, p. 16-pg., 2024-06-15.

Abstract

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)

• FAPESP's process: 14/02296-7 - Pharmacogenetics Manipulation and Research of Molecular Changes in Synapses between Selectively Activated Neurons in the Reinstatement of Ethanol Self-Administration
• Grantee: Rodrigo Molini Leão
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/24986-2 - The role of neuronal ensembles in context-induced reinstatement of ethanol seeking: pharmacogenetic, optogenetic and molecular investigation
• Grantee: Fabio Cardoso Cruz
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 18/15505-4 - Neurobiology study of relapse to alcohol and cocaine seeking: identification of plasticity in neuronal ensembles that encodes addiction-related memories
• Grantee: Fabio Cardoso Cruz
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2