Amphetamine‐stimulated dopamine release competes in vivo for [123I]IBZM binding to the D2 receptor in nonhuman primates
Amphetamine‐stimulated dopamine release competes in vivo for [123I]IBZM binding to the D2 receptor in nonhuman primates
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在非人灵长类动物中，安非他明刺激的多巴胺释放在体内竞争 [123I]IBZM 与 D2 受体的结合
作者：
R. Innis;R. Malison;M. Al;P. Hoffer;E. Sybirska;J. Seibyl;S. Zoghbi;R. Baldwin;M. Laruelle;Eileen O. Smith;D. Charney;G. Heninger;J. Elsworth;R. Roth
我们使用可逆结合的 D2 多巴胺受体放射性配体 [123I]IBZM（碘苯甲酰胺）来测试内源性神经递质多巴胺是否在体内竞争通过单光子发射计算机断层扫描 (SPECT) 测量的放射性示踪剂结合。在一系列非人类灵长类动物实验 (n = 27) 中，测量了温度、安非他明、氟哌啶醇和利血平对 [123I]IBZM 脑摄取的影响。 [123I]IBZM 的特定大脑摄取在注射放射性配体后 100 分钟达到峰值，并在接下来的 2 小时内表现出逐渐、明显的“稳态”冲洗。大脑的摄取与温度相关，在常温条件下（26%/小时：核心体温 35-37°C），特异性结合的放射性配体的洗脱率高于在受控低温条件下（11%/小时；32-34°C）。鉴于放射性保留率较高，所有其他实验均采用低温条件。在明显稳定状态期间给予氟哌啶醇（0.02 mg/kg IV）导致洗脱率急剧增加（60%/小时；p < 0.0001），与其有效的 D2 受体拮抗剂特性一致。 d-安非他明 (1.0 mg/kg IV) 对 D2 受体的亲和力可以忽略不计，但会介导内源性多巴胺储存的释放，也会增强洗脱作用 (34%/小时；p < 0.0005)。利血平预处理的剂量（1.0 mg/kg）足以导致纹状体多巴胺水平消耗超过 90%，阻止了这种安非他明增强的清除（10%/小时；p < 0.05）。利血平不能阻止直接作用的 D2 受体拮抗剂氟哌啶醇引起的洗脱增加。这些结果与以下假设一致：在使用 PET 和 SPECT 的神经受体成像研究中，内源性多巴胺可能有效地竞争体内放射性配体结合。
We used the reversibly binding D2 dopamine receptor radioligand [123I]IBZM (iodobenzamide) to test whether the endogenous neurotransmitter dopamine competes in vivo for radiotracer binding measured with single photon emission computed tomography (SPECT). In a series of nonhuman primate experiments (n = 27), the effects of temperature, amphetamine, haloperidol, and reserpine on brain uptake of [123I]IBZM were measured. Specific brain uptake of [123I]IBZM reached a peak by 100 min postinjection of radioligand and demonstrated a gradual, apparent “steady‐state” washout over the next 2 hr. Brain uptake was temperature dependent, with rates of washout of specifically bound radioligand greater under normothermic conditions (26%/hr: core body temperature 35–37°C) than under conditions of controlled hypothermia (11%/hr; 32–34°C). Given the greater retention of radioactivity, low‐temperature conditions were used in all other experiments. Administration of haloperidol (0.02 mg/kg IV) during the period of apparent steady state resulted in a dramatic increase in washout (60%/hr; p < 0.0001), consistent with its potent D2 receptor antagonist properties. d‐Amphetamine (1.0 mg/kg IV), which has negligible affinity for the D2 receptor but mediates the release of endogenous stores of dopamine, also enhanced washout (34%/hr; p < 0.0005). Reserpine pretreatment at doses (1.0 mg/kg) sufficient to cause greater than 90% depletion of striatal dopamine levels blocked this amphetamine‐enhanced washout (10%/hr; p < 0.05). Reserpine did not block the increased washout induced by the direct‐acting D2 receptor antagonist haloperidol. These results are consistent with the hypothesis that endogenous dopamine may effectively compete for radioligand binding in vivo in neuroreceptor imaging studies using PET and SPECT.
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影响因子：
56.9
作者：
KOOB, GF;BLOOM, FE
通讯作者：
BLOOM, FE
未使用抗精神病药的精神分裂症患者的 D2 多巴胺受体。
影响因子：
--
作者：
Farde,L;Wiesel,FA;Stone-Elander,S;Halldin,C;Nordström,AL;Hall,H;Sedvall,G
通讯作者：
Sedvall,G
[123I]IBZM 的体外和体内评估：一种潜在的 CNS D-2 多巴胺受体成像剂。
DOI：
--
发表时间：
1989
期刊：
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
影响因子：
--
作者：
Kung,HF;Pan,S;Kung,MP;Billings,J;Kasliwal,R;Reilley,J;Alavi,A
通讯作者：
Alavi,A
关于帕金森病病因的最新理论。
DOI：
10.1136/jnnp.52.suppl.13
发表时间：
1989
期刊：
Journal of neurology, neurosurgery, and psychiatry
影响因子：
--
作者：
Langston,JW
通讯作者：
Langston,JW
CNS D-2 多巴胺受体的体内 SPECT 成像：人体碘-123-IBZM 的初步研究。
DOI：
--
发表时间：
1990
期刊：
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
影响因子：
--
作者：
Kung,HF;Alavi,A;Chang,W;Kung,MP;KeyesJr,JW;Velchik,MG;Billings,J;Pan,S;Noto,R;Rausch
通讯作者：
Rausch