Melchor-Eixea Ignasi, Guarque-Chabrera Julian, Sanchez-Hernandez Aitor, Ibáñez-Marín Patricia, Pastor Raúl, Miquel Marta
Área de Psicobiología, Facultat de Ciències de la Salut, Universitat Jaume I, Castellón de la Plana, Spain.
Front Syst Neurosci. 2023 Jun 14;17:1154014. doi: 10.3389/fnsys.2023.1154014. eCollection 2023.
Substance Use Disorder (SUD) involves emotional, cognitive, and motivational dysfunction. Long-lasting molecular and structural changes in brain regions functionally and anatomically linked to the cerebellum, such as the prefrontal cortex, amygdala, hippocampus, basal ganglia, and ventral tegmental area, are characteristic of SUD. Direct and indirect reciprocal connectivity between the cerebellum and these brain regions can explain cerebellar roles in Pavlovian and reinforcement learning, fear memory, and executive functions. It is increasingly clear that the cerebellum modulates brain functions altered in SUD and other neuropsychiatric disorders that exhibit comorbidity with SUD. In the present manuscript, we review and discuss this evidence and present new research exploring the role of the cerebellum in cocaine-induced conditioned memory using chemogenetic tools (designer receptor exclusively activated by designer drug, DREADDs). Our preliminary data showed that inactivation of a region that includes the interposed and lateral deep cerebellar nuclei reduces the facilitating effect of a posterior vermis lesion on cocaine-induced preference conditioning. These findings support our previous research and suggest that posterior vermis damage may increase drug impact on the addiction circuitry by regulating activity in the DCN. However, they raise further questions that will also be discussed.
物质使用障碍（SUD）涉及情绪、认知和动机功能障碍。在功能和解剖学上与小脑相连的脑区，如前额叶皮质、杏仁核、海马体、基底神经节和腹侧被盖区，发生持久的分子和结构变化是SUD的特征。小脑与这些脑区之间直接和间接的相互连接可以解释小脑在经典条件反射和强化学习、恐惧记忆及执行功能中的作用。越来越清楚的是，小脑调节SUD及其他与SUD共病的神经精神疾病中改变的脑功能。在本手稿中，我们回顾并讨论了这一证据，并展示了使用化学遗传学工具（仅由设计药物激活的设计受体，DREADDs）探索小脑在可卡因诱导的条件性记忆中的作用的新研究。我们的初步数据表明，包括间位和外侧小脑深部核团的区域失活会降低小脑蚓部后部损伤对可卡因诱导的偏好条件反射的促进作用。这些发现支持了我们之前的研究，并表明小脑蚓部后部损伤可能通过调节深部小脑核团的活动来增加药物对成瘾回路的影响。然而，它们也提出了一些有待进一步讨论的问题。
