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

为了研究脑奖励系统随衰老的变化，采用体内微透析法测定了大鼠颅内自我刺激（ICSS）后脑单胺及其代谢物的变化。在幼年（4-6月龄）和老年（20-22月龄）F344大鼠下丘脑外侧植入ICSS电极，伏隔核植入透析探头插管。术后4 ~ 7天，在手术室内进行ICSS训练，直到动物有稳定的压杆反应，获得0.3秒的电刺激（100Hz脉冲），不引起运动障碍。第二天，我们进行了微透析实验，在ICSS阶段（1小时）以及ICSS前（1小时）和ICSS后（2小时）收集透析样本。在老年和年轻大鼠中，与基线水平相比，ICSS期间多巴胺（DA）释放增加了50%。另一方面，DA的代谢物DOPAC在幼龄大鼠中增加了基线水平的200%，而在老年大鼠中没有发现如此显著的增加。提高灌注液的钾浓度（钾负荷）有助于老年大鼠DA的释放。老龄大鼠钾负荷后DA代谢物减少程度较小，说明老龄大鼠DA摄取减少。结果表明：(1)ICSS行为随年龄变化不明显；(2)神经末梢DA摄取功能可能随年龄变化。老年动物多巴胺能末梢数量及其功能的变化有待进一步研究。

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.