Bickford P C, Adams C E, Boyson S J, Curella P, Gerhardt G A, Heron C, Ivy G O, Lin A M, Murphy M P, Poth K, Wallace D R, Young D A, Zahniser N R, Rose G M
Medical Research Service, Veterans Affairs Medical Center, Denver, CO 80220, USA.
Neurobiol Aging. 1997 May-Jun;18(3):309-18. doi: 10.1016/s0197-4580(97)80313-2.
L-Deprenyl (selegiline) was chronically administered to male Fischer 344 rats via their drinking water beginning at 54 weeks of age (estimated daily dose: 0.5 mg/kg/day). Beginning at 84 weeks of age, the rats were behaviorally evaluated using a sensorimotor battery, a motor-learning task, and the Morris water maze. At 118 weeks of age, cerebellar noradrenergic function was evaluated in the surviving rats using in vivo electrochemistry. The rats were then sacrificed to measure brain monoamine oxidase activity and perform quantitative autoradiography to evaluate the effect of chronic deprenyl treatment on beta-adrenergic receptors in the cerebellum, alpha 2-adrenergic receptors several brain regions, and D1 and D2 dopamine receptors in the striatum. Deprenyl treatment reduced brain monoamine oxidase B activity by 85%, but had no effect on brain monoamine oxidase A. A clear effect of chronic deprenyl treatment upon longevity was not observed. Several measures of CNS function were altered in the deprenyl-treated animals: 1) spatial learning in the Morris water maze was improved; 2) electrochemical signals recorded following local application of NE were reduced, and the responsiveness to the reuptake blocker nomifensine was enhanced, in the cerebellum; 3) beta-adrenergic receptor binding affinity was increased in the cerebellum; 4) alpha 2-adrenergic receptor density was increased in the inferior colliculus; and 5) striatal D1 dopamine receptor density was reduced but binding affinity was enhanced. In contrast, chronic deprenyl treatment did not cause changes in: 1) sensorimotor function, as evaluated by balance beam, inclined screen, or wire hang tasks; 2) motor learning; 3) alpha 2-adrenergic receptor density in any region examined except for the inferior colliculus, or binding affinity in any region examined; or 4) striatal D2 dopamine receptor number or affinity. Thus, long-term oral administration of deprenyl extended the functional life span of rats with respect to cognitive, but not motor, performance.
从54周龄开始，通过饮用水对雄性Fischer 344大鼠长期给予L - 司来吉兰（selegiline）（估计日剂量：0.5毫克/千克/天）。从84周龄开始，使用感觉运动功能组套、运动学习任务和莫里斯水迷宫对大鼠进行行为评估。在118周龄时，使用体内电化学方法对存活大鼠的小脑去甲肾上腺素能功能进行评估。然后处死大鼠，测量脑单胺氧化酶活性，并进行定量放射自显影，以评估长期给予司来吉兰对小脑β - 肾上腺素能受体、几个脑区的α2 - 肾上腺素能受体以及纹状体中D1和D2多巴胺受体的影响。司来吉兰治疗使脑单胺氧化酶B活性降低了85%，但对脑单胺氧化酶A没有影响。未观察到长期给予司来吉兰对寿命有明显影响。在接受司来吉兰治疗的动物中，中枢神经系统功能的几项指标发生了改变：1）莫里斯水迷宫中的空间学习能力得到改善；2）小脑局部应用去甲肾上腺素后记录的电化学信号降低，对再摄取阻断剂诺米芬辛的反应性增强；3）小脑中β - 肾上腺素能受体结合亲和力增加；4）下丘脑中α2 - 肾上腺素能受体密度增加；5）纹状体中D1多巴胺受体密度降低但结合亲和力增强。相比之下，长期给予司来吉兰并未导致以下变化：1）通过平衡木、倾斜屏幕或悬线任务评估的感觉运动功能；2）运动学习；3）除下丘体外任何检查区域的α2 - 肾上腺素能受体密度或任何检查区域的结合亲和力；或4）纹状体中D2多巴胺受体数量或亲和力。因此，长期口服司来吉兰可延长大鼠在认知方面而非运动方面的功能寿命。
