Fayle P, Jackson D M, Jenkins O F, Lafferty P A
Pharmacol Biochem Behav. 1985 Nov;23(5):715-20. doi: 10.1016/0091-3057(85)90060-7.
Mice were pretreated with haloperidol (HP) (3-4 mg/kg/day in drinking water) or vehicle for 21 days. On the 25th day, HP-pretreated mice were supersensitive to the locomotor stimulant effects of apomorphine (after acute premedication with reserpine and alpha-methyl-p-tyrosine). This behavioural supersensitivity was accompanied by a 25-39% increase in the number of [3H]-spiperone binding sites in the striata of HP-pretreated mice. Short-term repeated administration of the dopamine (DA) agonist drugs d-amphetamine and L-DOPA during the HP withdrawal phase (days 22, 23 and 24) had no effect on either measure of DA receptor supersensitivity. In contrast, the administration of apomorphine on days 22, 23 and 24 enhanced the HP-induced behavioural supersensitivity but decreased the HP-induced elevation of the number of [3H]-spiperone binding sites. Apomorphine treatment alone did not alter either measure. The results do not support the hypothesis that supersensitive DA receptors can be down-regulated by short-term treatment with DA agonist drugs and, moreover, indicate that important discrepancies may exist between behavioural and biochemical measures of DA receptor supersensitivity.
小鼠用氟哌啶醇（HP）（饮用水中3 - 4毫克/千克/天）或溶剂预处理21天。在第25天，经HP预处理的小鼠对阿扑吗啡的运动兴奋作用超敏感（在用利血平和α-甲基-对-酪氨酸进行急性预处理后）。这种行为超敏感性伴随着经HP预处理的小鼠纹状体中[3H]-司来吉兰结合位点数量增加25 - 39%。在HP撤药阶段（第22、23和24天）短期重复给予多巴胺（DA）激动剂药物d-苯丙胺和左旋多巴，对DA受体超敏感性的任何一项指标均无影响。相比之下，在第22、23和24天给予阿扑吗啡增强了HP诱导的行为超敏感性，但降低了HP诱导的[3H]-司来吉兰结合位点数量的升高。单独使用阿扑吗啡治疗未改变任何一项指标。结果不支持超敏DA受体可通过短期给予DA激动剂药物而下调的假说，此外，表明DA受体超敏感性的行为和生化指标之间可能存在重要差异。
