Department of Behavioral Neuroscience, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, 97239, USA; VA Portland Health Care System, 3710 SW US Veterans Hospital Rd, Portland, OR, 97239, USA.
Department of Behavioral Neuroscience, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, 97239, USA; VA Portland Health Care System, 3710 SW US Veterans Hospital Rd, Portland, OR, 97239, USA.
Neuropharmacology. 2022 Jul 1;212:109074. doi: 10.1016/j.neuropharm.2022.109074. Epub 2022 Apr 26.
Alcohol use disorder is a complex psychiatric disorder that can be modeled in rodents using a number of drinking paradigms. Drinking-in-the-dark (DID) is widely used to model the binge/intoxication stage of addiction, and chronic intermittent ethanol vapor procedures (CIE) are used to induce dependence and model withdrawal/negative affect induced escalation of drinking. We discuss experiments showing the ventral striatum (vStr) and extended amygdala (EA) are engaged in response to ethanol in rodents through c-Fos/Fos immunoreactivity studies. We also discuss experiments in rodents that span a wide variety of techniques where the function of vStr and EA structures are changed following DID or CIE, and the role of neurotransmitter and neuropeptide systems studies in these ethanol-related outcomes. We note where signaling systems converge across regions and paradigms and where there are still gaps in the literature. Dynorphin/κ-opioid receptor (KOR) signaling, as well as corticotropin releasing factor (CRF)/CRF receptor signaling were found to be important regulators of drinking behaviors across brain regions and drinking paradigms. Future research will require that females and a variety of rodent strains are used in preclinical experiments in order to strengthen the generalizability of findings and improve the likelihood of success for testing potential therapeutics in human laboratory studies.
酒精使用障碍是一种复杂的精神疾病，可以通过多种饮酒范式在啮齿动物中建模。暗饮（DID）广泛用于模拟成瘾的狂欢/醉酒阶段，慢性间歇性乙醇蒸气程序（CIE）用于诱导依赖并模拟戒断/负面情绪引发的饮酒增加。我们讨论了通过 c-Fos/Fos 免疫反应研究表明腹侧纹状体（vStr）和扩展杏仁核（EA）在啮齿动物对乙醇作出反应的实验。我们还讨论了在啮齿动物中进行的各种实验，其中 vStr 和 EA 结构的功能在 DID 或 CIE 后发生变化，以及神经递质和神经肽系统研究在这些与乙醇相关的结果中的作用。我们注意到信号系统在区域和范式上的汇聚点，以及文献中仍然存在的差距。强啡肽/κ-阿片受体（KOR）信号以及促肾上腺皮质释放因子（CRF）/CRF 受体信号被发现是跨脑区和饮酒范式调节饮酒行为的重要调节剂。未来的研究需要在临床前实验中使用女性和各种啮齿动物品系，以增强研究结果的普遍性，并提高在人类实验室研究中测试潜在治疗方法的成功率。
