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

为探讨脑奖赏系统随增龄的变化，采用在体微透析法测定了大鼠脑内单胺类物质及其代谢产物的变化。青年(4~6月龄)和老年(20~22月龄)F344大鼠在下丘脑外侧植入ICSS电极，在伏核植入透析探头套管。术后4~7d，在操作室开始ICSS训练，直至建立稳定的压杆反应，以获得不引起运动障碍的0.3s电刺激(100 Hz脉冲)。第二天进行微透析实验，分别于ICSS前(1h)、ICSS前(1h)和ICSS后(2h)采集透析样本，老年和青年大鼠ICSS期间多巴胺(DA)释放量均较基础水平增加50%。另一方面，多巴胺的代谢物DOPAC在年轻大鼠中增加了高达基线水平的200%，而在老年大鼠中没有检测到这种显著的增加。提高灌流液的钾浓度(钾负荷)可促进老年大鼠DA的释放。老年大鼠钾负荷后DA代谢产物减少的程度较小，提示老年大鼠对DA的摄取减少。结果提示：(1)ICSS行为随增龄变化不明显；(2)神经末梢DA摄取功能随增龄而改变。老年动物多巴胺能终末的数量及其功能的变化还有待进一步研究。

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.