Joseph J A, Kandasamy S B, Hunt W A, Dalton T K, Stevens S
Behavioral Sciences Department, Armed Forces Radiobiology Research Institute, Bethesda, MD 20814-5145.
Pharmacol Biochem Behav. 1988 Feb;29(2):335-41. doi: 10.1016/0091-3057(88)90166-9.
The effects of radiation exposure on haloperidol-induced catalepsy were examined in order to determine whether elevated prostaglandins, through an action on dopaminergic autoreceptors, could be involved in the radiation-induced increase in the potency of this neuroleptic. Cataleptic behavior was examined in animals irradiated with various doses of gamma photons (1-150 Gy) and pretreated with a subthreshold dose of haloperidol (0.1 mg/kg). This approach was chosen to maximize any synergistic effects of radiation and haloperidol. After irradiation with doses less than or equal to 30 Gy, the combined treatment of haloperidol and radiation produced catalepsy, whereas neither treatment alone had an effect. This observed catalepsy could be blocked with prior administration of indomethacin, a prostaglandin synthesis inhibitor. Animals exposed to doses of radiation less than or equal to 50 Gy and no haloperidol, however, displayed apparent catalepsy. This effect was also antagonized by indomethacin. Prostaglandins can induce catalepsy and when administered in subthreshold doses along with subthreshold doses of haloperidol, catalepsy was observed. In order to assess a possible action of prostaglandins and radiation on dopaminergic activity, the functioning of striatal dopaminergic autoreceptors was examined by determining the effects of varying concentrations of haloperidol on the K+-evoked release of dopamine from striatal slices obtained from parallel groups of animals treated as above. Results indicated that sensitivity to haloperidol increased (higher K+-evoked dopamine release) in slices from irradiated or prostaglandin-treated animals and that this increase in sensitivity was blocked by indomethacin. Results from both experiments suggest that radiation-induced increases in endogenous neuronal mediators, such as prostaglandins, can induce catalepsy through an action on dopaminergic autoreceptors.
为了确定升高的前列腺素是否通过作用于多巴胺能自身受体而参与辐射诱导的这种抗精神病药物效力增加，研究了辐射暴露对氟哌啶醇诱导的僵住症的影响。在接受不同剂量γ光子（1 - 150 Gy）照射并用亚阈值剂量氟哌啶醇（0.1 mg/kg）预处理的动物中检查僵住行为。选择这种方法是为了最大化辐射和氟哌啶醇的任何协同作用。用小于或等于30 Gy的剂量照射后，氟哌啶醇和辐射的联合治疗产生了僵住症，而单独任何一种治疗都没有效果。这种观察到的僵住症可以被预先给予的前列腺素合成抑制剂吲哚美辛阻断。然而，暴露于小于或等于50 Gy辐射且未用氟哌啶醇处理的动物表现出明显的僵住症。这种效应也被吲哚美辛拮抗。前列腺素可以诱导僵住症，当与亚阈值剂量的氟哌啶醇一起以亚阈值剂量给药时，观察到了僵住症。为了评估前列腺素和辐射对多巴胺能活性的可能作用，通过确定不同浓度的氟哌啶醇对从上述平行组动物获得的纹状体切片中钾离子诱发的多巴胺释放的影响，来检查纹状体多巴胺能自身受体的功能。结果表明，在来自接受辐射或前列腺素处理的动物的切片中，对氟哌啶醇的敏感性增加（更高的钾离子诱发的多巴胺释放），并且这种敏感性增加被吲哚美辛阻断。两个实验的结果都表明，辐射诱导的内源性神经元介质如前列腺素的增加可以通过作用于多巴胺能自身受体来诱导僵住症。
