Psychophysiological studies on function of brain reward system in aged animals.

老年动物大脑奖赏系统功能的心理生理学研究。

• 批准号: 03451013
• 负责人: IWASAKI Tsuneo
• 金额: $ 3.52万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-03451013/
• 关键词: aging; brain microdialysis; brain self-stimulation; brain reward system; rat; 加齢; 脳内報酬系; 脳内自己刺激; マイクロ・ダイアリシス; 脳内伝達物質; メタンフェタミン

In order to investigate the changes of brain reward system with aging, brain monoamines and their metabolites of rats performing intracranial self-stimulation (ICSS) had been measured using in vivo microdialysis. Young (4-6 months old) and aged (20-22 months old) F344 rats were implanted with ICSS electrodes in the lateral hypothalamus and with cannula for dialysis probes in the nucleus accumbens. Four to 7 days after operation, ICSS training in an operant chamber began, and continued until the animal's stable lever-pressing response to obtain 0.3sec electrical stimulation (100Hz pulse) which did not induce motor disturbance had been established. On the next day we conducted the microdialysis experiment, in which dialysis samples were collected during ICSS session (1h) as well as pre-(1h) and post-ICSS (2h) sessions.In both aged and young rats, dopamine (DA) release increased by 50% during ICSS session compared with that of baseline level. On the other hand, DOPAC, an metabolite of DA, increased up to 200% of baseline level in young rats, while such a significant increase was not detected in aged rats. Raising the potassium concentration of the perfusate (potassium loading) facilitated DA release in aged rats. Degree of decrease in DA metabolites after potassium loading was smaller in aged rats, indicating the decrease of DA uptake in those rats. Results suggest that (1) ICSS behavior does not show clear change with aging, and (2) DA uptake function in nerve terminals may change with aging. Further research is needed to clarify the changes of the number of dopaminergic terminals and their function in aged animals.

为探讨脑奖赏系统随增龄的变化，采用在体微透析技术测定了颅内自我刺激（ICSS）大鼠脑内单胺类递质及其代谢产物的含量。将年轻（4-6月龄）和老年（20-22月龄）F344大鼠在外侧下丘脑中植入ICSS电极，并在延髓核中植入用于透析探针的套管。术后4 ~ 7天，在操作室中开始ICSS训练，并持续到动物获得稳定的0.3秒电刺激（100 Hz脉冲）的按压反应，该反应不会引起运动障碍。第二天进行微透析实验，收集ICSS期间（1h）、ICSS前（1h）和ICSS后（2 h）的透析样品，结果显示，老年和青年大鼠ICSS期间多巴胺（DA）释放量较基线水平增加50%。另一方面，多巴胺的代谢产物DOPAC在年轻大鼠中增加至基线水平的200%，而在老年大鼠中未检测到这种显著增加。提高钾离子浓度的灌流液（钾负荷）促进DA释放老年大鼠。钾负荷后DA代谢产物的减少程度在老年大鼠中较小，表明这些大鼠中DA摄取的减少。结果提示：（1）ICSS行为无明显增龄性变化;（2）神经末梢DA摄取功能可能随增龄而改变。多巴胺能神经末梢在老年动物中数量的变化及其功能有待进一步研究。

项目成果

Nakahara,D.: "Differential effect selfーstimulation on dopamine release and metabolism in the rat medial frontex,nucleus accumbens and striatum studied by in vivo microdialysis." Brain Research. (1992)

Nakahara, D.：“通过体内微透析研究自我刺激对大鼠内侧额叶、伏隔核和纹状体多巴胺释放和代谢的差异影响”(1992)。