Morelli M, Fenu S, Di Chiara G
Institute of Pharmacology and Experimental Toxicology, University of Cagliari, Italy.
Brain Res. 1989 May 15;487(1):120-30. doi: 10.1016/0006-8993(89)90947-5.
Opioid agonists having different affinity for delta and mu receptors were injected bilaterally in the substantia nigra (SN) of rats. The selective agonist of mu receptors N-MePhe3,-D-Pro4 morphiceptin (PLO 17) produced a stereotyped behavior characterized by stereotyped sniffing and gnawing antagonized by the irreversible antagonist of mu receptors beta-funaltrexamine. In contrast, bilateral intranigral injection of the selective delta agonist D-Pen2,D-Pen5 enkephalin (DPDPE) elicited dose-dependent exploratory behavior and rearing but failed to produce gnawing. The behavioral syndrome induced by DPDPE was significantly reduced by the selective delta antagonist ICI 174,864. Naloxine, a non-selective opioid antagonist, antagonized the effects of both compounds. SCH 23390 and haloperidol, two antagonists of dopaminergic D1 and D2 receptors, respectively, blocked the effects of PLO 17 and DPDPE. The results indicate that stimulation of specific opioid receptor types in the SN elicits specific behavioral syndromes and suggest that the SN might be the site of origin of certain items of the behavioral syndrome evoked by systemic opiates. These items might be mediated by activation of dopaminergic neurons of the ventral mesencephalon.
对δ和μ受体具有不同亲和力的阿片类激动剂双侧注射到大鼠黑质(SN)中。μ受体的选择性激动剂N-甲基苯丙氨酸3,-D-脯氨酸4吗啡脑啡肽(PLO 17)产生一种刻板行为,其特征为刻板的嗅探和啃咬,可被μ受体的不可逆拮抗剂β-芬太尼丁拮抗。相比之下,双侧黑质内注射选择性δ激动剂D-青霉胺2,D-青霉胺5脑啡肽(DPDPE)引发剂量依赖性的探究行为和竖毛,但未产生啃咬行为。选择性δ拮抗剂ICI 174,864可显著减轻DPDPE诱导的行为综合征。纳洛酮,一种非选择性阿片类拮抗剂,可拮抗这两种化合物的作用。SCH 23390和氟哌啶醇,分别为多巴胺能D1和D2受体的两种拮抗剂,可阻断PLO 17和DPDPE的作用。结果表明,刺激黑质中特定类型的阿片受体可引发特定的行为综合征,并提示黑质可能是全身阿片类药物诱发的行为综合征某些项目的起源部位。这些项目可能由腹侧中脑多巴胺能神经元的激活介导。