Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
CIBER de Salud Mental (CIBERSAM), Madrid, Spain.
Sci Rep. 2022 Mar 17;12(1):4643. doi: 10.1038/s41598-022-08698-9.
Vulnerability to addiction may be given by the individual's risk of developing an addiction during their lifetime. A challenge in the neurobiology of drug addiction is understanding why some people become addicted to drugs. Here, we used positron emission tomography (PET) and statistical parametric mapping (SPM) to evaluate changes in brain glucose metabolism in response to chronic morphine self-administration (MSA) in two rat strains with different vulnerability to drug abuse, Lewis (LEW) and Fischer 344 (F344). Four groups of animals were trained to self-administer morphine or saline for 15 days. 2-deoxy-2-[F]-fluoro-D-glucose (FDG)-PET studies were performed on the last day of MSA (acquisition phase) and after 15 days of withdrawal. PET data were analyzed using SPM12. LEW-animals self-administered more morphine injections per session than F344-animals. We found significant brain metabolic differences between LEW and F344 strains in the cortex, hypothalamus, brainstem, and cerebellum. In addition, the different brain metabolic patterns observed after the MSA study between these rat strains indicate differences in the efficiency of neural substrates to translate the drug effects, which could explain the differences in predisposition to morphine abuse between one individual and another. These findings have important implications for the use of these rat strains in translational morphine and opiate research.
成瘾易感性可能由个体在其一生中发展成瘾的风险决定。药物成瘾的神经生物学中的一个挑战是理解为什么有些人会对药物上瘾。在这里,我们使用正电子发射断层扫描 (PET) 和统计参数映射 (SPM) 来评估两种对滥用药物易感性不同的大鼠品系(LEW 和 Fischer 344 [F344])在慢性吗啡自我给药 (MSA) 后大脑葡萄糖代谢的变化。四组动物接受吗啡或生理盐水自我给药训练 15 天。在 MSA 的最后一天(获取阶段)和戒断 15 天后进行 2-脱氧-2-[F]-氟-D-葡萄糖 (FDG)-PET 研究。使用 SPM12 分析 PET 数据。LEW 动物每节自我给药的吗啡注射次数多于 F344 动物。我们发现 LEW 和 F344 品系之间在皮质、下丘脑、脑干和小脑之间存在明显的大脑代谢差异。此外,这些大鼠品系在 MSA 研究后观察到的不同大脑代谢模式表明,神经基质将药物作用转化为不同效率的差异,这可以解释个体之间对吗啡滥用的倾向差异。这些发现对这些大鼠品系在吗啡和阿片类药物的转化研究中的应用具有重要意义。