Pizzolato G, Soncrant T T, Holloway H W, Rapoport S I
J Neurosci. 1985 Nov;5(11):2831-8. doi: 10.1523/JNEUROSCI.05-11-02831.1985.
Local cerebral glucose utilization (LCGU) was determined in 49 brain regions of 3-, 12-, 24-, and 33-month-old awake Fischer-344 rats, at 30 to 120 min after administration of the dopaminergic antagonist haloperidol (HAL) at 1 mg/kg (i.p.). The quantitative autoradiographic [14C]-2-deoxyglucose technique was employed. In 3-month rats, HAL produced statistically significant (p less than 0.05) reductions in LCGU in 63% of the brain regions examined, including those having dopaminergic as well as non-dopaminergic function. With increasing age, LCGU was progressively less affected by HAL. Significant declines in LCGU occurred in 21 to 23% of the observed regions in 12- and 24-month rats, and in 10% of the 49 regions in 33-month-old rats. The peak effects of HAL on LCGU occurred later in the 33-month- than in the 3-month-old rats (90 and 60 min after HAL, respectively). The behavioral effect (catalepsy) of HAL was less in old than in young rats. Age-related differences in the cerebral metabolic and behavioral responsivities of rats to HAL are not due to differences in brain concentrations of HAL, as higher concentrations are obtained in older animals (Kapetanovic, I.M., D.J. Sweeney, and S.I. Rapoport (1982) J. Pharmacol. Exp. Ther. 221: 434-438). The differences correlate with known age-dependent structural and biochemical deficits of the central dopaminergic system and indicate reduced functioning of that system in the rat brain after 12 months of age.
在3、12、24和33月龄的清醒Fischer-344大鼠的49个脑区中，于腹腔注射1mg/kg多巴胺能拮抗剂氟哌啶醇（HAL）后30至120分钟测定局部脑葡萄糖利用率（LCGU）。采用定量放射自显影[14C]-2-脱氧葡萄糖技术。在3月龄大鼠中，HAL使63%的被检测脑区的LCGU出现统计学显著降低（p<0.05），包括那些具有多巴胺能和非多巴胺能功能的脑区。随着年龄增长，LCGU受HAL的影响逐渐减小。在12和24月龄大鼠中，21%至23%的观察区域的LCGU出现显著下降，在33月龄大鼠的49个区域中有10%出现下降。HAL对LCGU的峰值效应在33月龄大鼠中比在3月龄大鼠中出现得更晚（分别在HAL给药后90分钟和60分钟）。HAL的行为效应（僵住症）在老年大鼠中比在幼年大鼠中更小。大鼠对HAL的脑代谢和行为反应性的年龄相关差异并非由于脑中HAL浓度的差异，因为老年动物中的HAL浓度更高（卡佩塔诺维奇，I.M.，D.J.斯威尼，和S.I.拉波波特（1982年）《药理学与实验治疗学杂志》221：434 - 438）。这些差异与已知的中枢多巴胺能系统随年龄变化的结构和生化缺陷相关，并表明12月龄后大鼠脑中该系统功能降低。
