Costentin J, Duterte-Boucher D, Panissaud C, Michael-Titus A
Unité de Neuropsychopharmacologie expérimentale, U.R.A., C.N.R.S.-Faculté de Médecine, Saint-Etienne du Rouvray, France.
Neuropharmacology. 1990 Jan;29(1):31-5. doi: 10.1016/0028-3908(90)90080-b.
In mice, rendered poikilothermic by a prior (18 hr) subcutaneous administration of reserpine (3 mg/kg), the subcutaneous administration of apomorphine increased dose-dependently the body temperature. This effect was potentiated by the specific D2 dopamine antagonist sulpiride. On the contrary, it was reduced by the specific D1 dopamine antagonist SCH 23390. A desensitization of D2 receptors was produced by the repeated administration of the specific D2 agonist RU 24926. This pretreatment led to an increased efficacy of apomorphine in antagonizing reserpine-induced hypothermia. Similarly, a desensitization of D1 receptors was created by the repeated administration of the specific D1 agonist CY 208-243. This pretreatment significantly diminished the efficacy of apomorphine in antagonizing reserpine-induced hypothermia. The repeated administration of the D1 agonist CY 208-243, in non-reserpinized mice, significantly increased the hypothermic effect of apomorphine (1 mg/kg). Thus, it appears that, in normal mice, but especially in reserpinized mice, the stimulation of D1 receptors by apomorphine induces an increase in body temperature that is masked, especially in normal mice, by the hypothermic effect, resulting from the simultaneous stimulation of D2 receptors.
给小鼠预先皮下注射利血平(3毫克/千克)使其体温调节功能丧失,再皮下注射阿扑吗啡,其体温会随剂量增加而升高。特异性D2多巴胺拮抗剂舒必利可增强此效应。相反,特异性D1多巴胺拮抗剂SCH 23390则会减弱此效应。重复给予特异性D2激动剂RU 24926会导致D2受体脱敏。这种预处理会使阿扑吗啡拮抗利血平诱导的体温过低的效果增强。同样,重复给予特异性D1激动剂CY 208 - 243会导致D1受体脱敏。这种预处理会显著降低阿扑吗啡拮抗利血平诱导的体温过低的效果。在未注射利血平的小鼠中,重复给予D1激动剂CY 208 - 243会显著增强阿扑吗啡(1毫克/千克)的降温效果。因此,在正常小鼠中,尤其是注射了利血平的小鼠中,阿扑吗啡对D1受体的刺激会导致体温升高,但这种升高在正常小鼠中尤其会被同时刺激D2受体所产生的降温效应掩盖。