Tomazi Lediane, Mello Carlos Fernando, Schöffer Ana Paula, Girardi Bruna Amanda, Frühauf Pâmella Karina Santana, Rubin Maribel Antonello
Graduation Program in Pharmacology, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil.
Biochemistry and Molecular Biology Department, Natural and Exact Sciences Center, Federal University of Santa Maria, Santa Maria, RS, Brazil, 97105-900.
Mol Neurobiol. 2017 Jan;54(1):710-721. doi: 10.1007/s12035-015-9678-0. Epub 2016 Jan 14.
N-methyl-D-aspartate (NMDA) receptor antagonists block morphine-induced conditioned place preference (CPP). Although polyamines are endogenous modulators of the NMDA receptor, it is not known whether polyaminergic agents induce CPP or modulate morphine-induced CPP. Here, we examined whether polyamine ligands modify morphine CPP acquisition, consolidation, and expression. Adult male albino Swiss mice received saline (0.9 % NaCl, intraperitoneally (i.p.)) or morphine (5 mg/kg, i.p.) and were respectively confined to a black or a white compartment for 30 min for four consecutive days for CPP induction. The effect of arcaine (3 mg/kg, i.p.) or spermidine (30 mg/kg, i.p.), respectively, an antagonist and an agonist of the polyamine-binding site at the NMDA receptor, on the acquisition, consolidation, and expression of morphine CPP was studied. In those experiments designed to investigate whether spermidine prevented or reversed the effect of arcaine, spermidine (30 mg/kg, i.p.) was administered 15 min before or 15 min after arcaine, respectively. Arcaine and spermidine did not induce CPP or aversion per se. Arcaine (3 mg/kg, i.p.) impaired the acquisition, consolidation, and expression of morphine CPP. Spermidine prevented the impairing effect of arcaine on the acquisition of morphine CPP but not the impairing effect of arcaine on consolidation or expression of morphine CPP. These results suggest that arcaine may impair morphine CPP acquisition by modulating the polyamine-binding site at the NMDA receptor. However, the arcaine-induced impairment of consolidation and expression of morphine CPP seems to involve other mechanisms.
N-甲基-D-天冬氨酸（NMDA）受体拮抗剂可阻断吗啡诱导的条件性位置偏爱（CPP）。尽管多胺是NMDA受体的内源性调节剂，但尚不清楚多胺能药物是否会诱导CPP或调节吗啡诱导的CPP。在此，我们研究了多胺配体是否会改变吗啡CPP的获得、巩固和表达。成年雄性白化瑞士小鼠接受生理盐水（0.9% NaCl，腹腔注射（i.p.））或吗啡（5 mg/kg，i.p.），并分别连续四天每天在黑色或白色隔室中禁闭30分钟以诱导CPP。研究了阿卡因（3 mg/kg，i.p.）或亚精胺（30 mg/kg，i.p.）分别作为NMDA受体多胺结合位点的拮抗剂和激动剂对吗啡CPP获得、巩固和表达的影响。在旨在研究亚精胺是否预防或逆转阿卡因作用的实验中，亚精胺（30 mg/kg，i.p.）分别在阿卡因前15分钟或后15分钟给药。阿卡因和亚精胺本身不会诱导CPP或厌恶。阿卡因（3 mg/kg，i.p.）损害吗啡CPP的获得、巩固和表达。亚精胺可预防阿卡因对吗啡CPP获得的损害作用，但不能预防阿卡因对吗啡CPP巩固或表达的损害作用。这些结果表明，阿卡因可能通过调节NMDA受体的多胺结合位点来损害吗啡CPP的获得。然而，阿卡因诱导的吗啡CPP巩固和表达的损害似乎涉及其他机制。
