Frey J M, Morgan W W, Ticku M K, Huffman R D
Pharmacol Biochem Behav. 1987 Apr;26(4):661-9. doi: 10.1016/0091-3057(87)90593-4.
The induction of dopaminergic supersensitivity in rats by the administration of haloperidol in their diet for 30 days (CHAL) in three increasing concentrations (7-15 mg/kg/day) was compared to that induced by single daily subcutaneous injections (SCHAL, 0.7 mg/kg) on the basis of biochemical (radioimmunoassay of serum haloperidol levels, 3H-spiroperidol binding) or behavioral (apomorphine stereotypy, spontaneous locomotor activity) parameters. The two modes of administration produced equivalent blood levels of haloperidol by day 30. At 48 hours post treatment: spontaneous locomotor activity and stereotyped behavior were significantly increased in both groups of haloperidol-treated rats, stereotyped behavior was significantly greater in CHAL- vs. SCHAL-treated rats at 8 days post treatment and specific 3H-spiroperidol binding was increased 64% and 236% within the striatum and GP, respectively, of CHAL-treated vs. control rats. Scatchard analysis of 3H-spiroperidol binding isotherms revealed a significant increase in the Bmax of high affinity binding sites [KD approximately 55 pM] within the striatum of both CHAL- and SCHAL-treated rats at 48 hours post treatment. A second, lower affinity site was resolved within the SCHAL-treated group which was not detected within striatal homogenates of CHAL-treated or control rats.
将三种递增浓度（7 - 15毫克/千克/天）的氟哌啶醇添加到大鼠饮食中30天（慢性氟哌啶醇给药，CHAL）所诱导的多巴胺能超敏反应，与每日单次皮下注射（单次皮下氟哌啶醇给药，SCHAL，0.7毫克/千克）所诱导的多巴胺能超敏反应相比较，比较基于生化参数（血清氟哌啶醇水平的放射免疫测定、3H-螺哌啶醇结合）或行为参数（阿扑吗啡刻板行为、自发运动活性）。到第30天时，两种给药方式产生的氟哌啶醇血药浓度相当。治疗后48小时：两组氟哌啶醇处理的大鼠自发运动活性和刻板行为均显著增加，治疗后8天，CHAL处理组大鼠的刻板行为显著大于SCHAL处理组大鼠，CHAL处理组大鼠纹状体和苍白球内的特异性3H-螺哌啶醇结合分别比对照组增加了64%和236%。对3H-螺哌啶醇结合等温线的Scatchard分析显示，治疗后48小时，CHAL处理组和SCHAL处理组大鼠纹状体内高亲和力结合位点[解离常数（KD）约为55皮摩尔]的最大结合量（Bmax）均显著增加。在SCHAL处理组中解析出了第二个亲和力较低的位点，而在CHAL处理组或对照组大鼠的纹状体匀浆中未检测到该位点。
