Bianchi Paula Cristina, Palombo Paola, Engi Sheila Antonagi, Carneiro de Oliveira Paulo Eduardo, Tavares Gabrielle Emily Boaventura, Anjos-Santos Alexia, Yokoyama Thais Suemi, Planeta Cleopatra da Silva, Cruz Fábio Cardoso, Leão Rodrigo Molini
Laboratory of Behavioral Neuroscience, Paulista Medicine School, Universidade Federal de São Paulo-UNIFESP, São Paulo, SP, Brazil.
Laboratory of Neuropsychopharmacology, School of Pharmaceutical Sciences, São Paulo State University, UNESP, Araraquara, SP, Brazil.
Brain Res. 2024 Oct 15;1841:149086. doi: 10.1016/j.brainres.2024.149086. Epub 2024 Jun 12.
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 Fos-immunohistochemistry 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.
酒精使用障碍(AUD)仍是全球一个关键的公共卫生问题,其特征是复发率高,且常由情境线索引发。本研究调查情境诱导的觅酒行为恢复背后的神经机制,重点关注伏隔核及其与前额叶皮质的相互作用,采用雄性Long-Evans大鼠进行ABA恢复模型实验。在我们的实验设置中,大鼠在情境A中接受训练以自我给药10%的乙醇,随后在情境B中存在离散线索的情况下消退压杆行为。然后通过在消退条件下将大鼠重新暴露于情境A或B来评估情境诱导的觅酒行为恢复,旨在模拟环境线索对复发行为的影响。进行了三项实验:实验1利用Fos免疫组织化学检查伏隔核中的神经元激活;实验2应用巴氯芬+蝇蕈醇失活技术探究伏隔核核心的功能重要性;实验3使用Fos免疫荧光结合逆行珠注射来研究从前额叶皮质投射到伏隔核核心的神经元的激活。我们的研究结果显示,在情境A的恢复阶段,伏隔核核心和壳内Fos免疫反应性核显著增加,突出了环境对觅酒行为的强大影响。此外,伏隔核核心的失活显著降低了恢复,并且在与乙醇相关的情境中,从前额叶皮质到伏隔核核心的神经元有明显激活。这些结果突出了伏隔核核心及其皮质纹状体投射在情境驱动的觅酒神经回路中的关键作用。
Psychopharmacology (Berl). 2016-5