Polgár K, Máté I, Till M, Székely J I
Institute for Drug Research, Budapest, Hungary.
Neuropharmacology. 1987 Sep;26(9):1309-14. doi: 10.1016/0028-3908(87)90092-x.
The aim of the present investigation was to examine which areas of the brain might mediate the anti-apomorphine action of some opioids, which were found previously to be active upon subcutaneous application. As the first step, the substances were injected intracerebroventricularly or into the nucleus accumbens, a mesolimbic region which is rich in dopamine, and the inhibition of stereotypy induced by apomorphine was quantified. In a separate group of animals (rats with unilateral lesion of the nigra) the antagonism of turning behaviour elicited by apomorphine was measured. Substances examined were morphine, a mu-selective opiate; D-Ala2,Nle5-enkephalin sulphonic acid (ES), a delta-selective opioid peptide; D-Met2,Pro5-enkephalinamide (EA), a highly potent but non-selective opioid; and two dopamine receptor blockers, haloperidol and chlorpromazine, for comparison. Examining the antagonism of turning behaviour induced by apomorphine, the order of potency was EA greater than haloperidol greater than morphine greater than ES approximately equal to chlorpromazine if injections of the substances were intracerebroventricular and EA greater than morphine much greater than haloperidol approximately equal to ES much greater than chlorpromazine when administered into the nucleus accumbens. The order of potency for the suppression of stereotypy induced by apomorphine was EA much greater than haloperidol greater than morphine greater than ES greater than chlorpromazine upon intracerebroventricular application and EA much greater than haloperidol greater than morphine ES greater than chlorpromazine if injected into the nucleus accumbens. The data indicate that endogenous opioids might inhibit the activity of dopamine in brain through the nucleus accumbens.
本研究的目的是探究大脑的哪些区域可能介导某些阿片类药物的抗阿扑吗啡作用，这些阿片类药物先前已被发现皮下给药时有活性。第一步，将这些物质脑室内注射或注射到伏隔核（一个富含多巴胺的中脑边缘区域），并对阿扑吗啡诱导的刻板行为抑制进行量化。在另一组动物（黑质单侧损伤的大鼠）中，测量阿扑吗啡引起的旋转行为的拮抗作用。所检测的物质有吗啡（一种μ选择性阿片类药物）；D - Ala2，Nle5 - 脑啡肽磺酸（ES，一种δ选择性阿片肽）；D - Met2，Pro5 - 脑啡肽酰胺（EA，一种高效但非选择性的阿片类药物）；以及两种多巴胺受体阻滞剂氟哌啶醇和氯丙嗪用于比较。检查阿扑吗啡诱导的旋转行为的拮抗作用时，如果将这些物质脑室内注射，效力顺序为EA＞氟哌啶醇＞吗啡＞ES≈氯丙嗪；如果注射到伏隔核，则效力顺序为EA＞吗啡＞＞氟哌啶醇≈ES＞＞氯丙嗪。阿扑吗啡诱导的刻板行为抑制的效力顺序为：脑室内给药时EA＞＞氟哌啶醇＞吗啡＞ES＞氯丙嗪；注射到伏隔核时EA＞＞氟哌啶醇＞吗啡＞ES＞氯丙嗪。数据表明内源性阿片类药物可能通过伏隔核抑制大脑中多巴胺的活性。
