Soncrant T T, Holloway H W, Greig N H, Rapoport S I
Laboratory of Neurosciences, National Institute on Aging, Bethesda, MD 20892.
Brain Res. 1989 May 22;487(2):255-66. doi: 10.1016/0006-8993(89)90830-5.
In order to determine whether a functional deficit in brain cholinoception accompanies the reported loss of muscarinic receptors with age, local cerebral glucose utilization (LCGU) was measured in awake 3- and 24-month-old rats after the administration of the muscarinic cholinergic agonist arecoline. Awake, male Fischer-344 rats received isotonic saline or arecoline (0.05-50 mg/kg), i.p., and LCGU was measured in 95 regions with the [14C]2-deoxy-D-glucose technique. Plasma and brain pharmacokinetics of arecoline in rats of both ages were measured in a separate experiment and were found not to differ between the two age groups. Peak cerebral cortex arecoline concentrations, at 3 min after the administration of 5 mg/kg, i.p., were 1558 +/- 588 and 1830 +/- 317 ng/g in 3- and 24-month-old rats, respectively. LCGU effects were dose-dependent, with fewer regions activated by smaller doses. In 24-month-old rats, arecoline in one or more doses elevated LCGU significantly in 94% of the regions examined; no declines in LCGU were found. Increases in whole brain glucose utilization produced by all doses of arecoline, compared to control values, were similar in 3- and 24-month-old rats. After one or more doses, the rise in LCGU in 24-month-old animals, compared to that in 3-month rats, was not significantly different in 75 brain regions, greater in 13 and smaller in 7. These findings demonstrate that the functional responsivity of brain regions to a cholinergic agonist is, for the most part, age-invariant in the rat, implying that the function of muscarinic receptor and postreceptor mechanisms remains intact despite reported age-related losses of muscarinic receptors.
为了确定随着年龄增长所报道的毒蕈碱受体丧失是否伴随着脑胆碱感受功能缺陷，在清醒的3月龄和24月龄大鼠腹腔注射毒蕈碱胆碱能激动剂槟榔碱后，测量局部脑葡萄糖利用率（LCGU）。清醒的雄性Fischer-344大鼠腹腔注射等渗盐水或槟榔碱（0.05 - 50mg/kg），采用[14C]2-脱氧-D-葡萄糖技术在95个区域测量LCGU。在另一个实验中测量了两个年龄组大鼠血浆和脑内槟榔碱的药代动力学，发现两个年龄组之间没有差异。腹腔注射5mg/kg槟榔碱后3分钟，3月龄和24月龄大鼠大脑皮层槟榔碱的峰值浓度分别为1558±588和1830±317ng/g。LCGU效应呈剂量依赖性，较小剂量激活的区域较少。在24月龄大鼠中，一种或多种剂量的槟榔碱使94%的检测区域LCGU显著升高；未发现LCGU下降。与对照值相比，所有剂量的槟榔碱引起的全脑葡萄糖利用率增加在3月龄和24月龄大鼠中相似。一种或多种剂量后，与3月龄大鼠相比，24月龄动物LCGU的升高在75个脑区无显著差异，在13个脑区升高更大，在7个脑区升高更小。这些发现表明，在大鼠中，脑区对胆碱能激动剂的功能反应性在很大程度上不随年龄变化，这意味着尽管有报道称毒蕈碱受体与年龄相关的丧失，但毒蕈碱受体和受体后机制的功能仍然完好无损。
