There is accumulating evidence supporting the involvement of tissue-plasminogen activator (tPA) in the mechanisms underlying the effects of morphine and an enriched environment. This study was designed to investigate possible interactive roles of the glutamatergic and the dopaminergic systems regarding hippocampal tPA in the neurobiology of morphine dependence. For this purpose, Wistar albino rats, housed in either a standard- (SE) or an enriched environment (EE) were implanted subcutaneously with morphine (150 mg base) or placebo pellets. Behavioral and somatic signs of morphine abstinence precipitated by an opioid-receptor antagonist naloxone (1 mg/kg, i.p.) 72 h after the pellet implantation were observed individually for 15 min in all groups. Memantine (10 mg/kg i.p.), an antagonist of N-methyl-D-aspartic acid class of glutamatergic receptor-subtype decreased teeth-chattering, ptosis, diarrhea and the loss of body weight. SKF82958 (1 mg/kg, i.p.), a dopamine D1-receptor agonist decreased jumping and ptosis but increased rearing and loss of body weight. On the other hand, co-administration of SKF82958 with memantine prevented some of their effects that occur when administered alone at the same doses. Furthermore, the EE did not change the intensity of morphine abstinence. The level of hippocampal tPA mRNA was found to be lower in the SE morphine abstinence group than in the placebo group and close to the EE morphine abstinence group, whereas there was no significant alteration of its level in the memantine or SKF82958 groups. These findings suggest that the interaction between the glutamatergic and the dopaminergic systems may be an important component of the neurobiology of morphine dependence, and the role of tPA in this interaction should be further investigated.

越来越多的证据支持组织纤溶酶原激活剂 (tPA) 参与吗啡和丰富环境的作用机制。本研究旨在探讨海马 tPA 的谷氨酸能系统和多巴胺能系统在吗啡依赖的神经生物学中可能的相互作用。为此，将饲养在标准环境 (SE) 或丰富环境 (EE) 中的Wistar 白化大鼠皮下植入吗啡（150 毫克碱）或安慰剂颗粒。在颗粒植入后 72 小时，在所有组中单独观察 15 分钟，由阿片受体拮抗剂纳洛酮（1 mg/kg，腹膜内注射）引发吗啡戒断的行为和躯体症状。美金刚（10 mg/kg ip）是一种谷氨酸受体亚型N-甲基-D-天冬氨酸类拮抗剂，可减少牙齿打颤、下垂、腹泻和体重减轻。SKF82958（1 mg/kg，腹腔注射）是一种多巴胺 D1 受体激动剂，可减少跳跃和下垂，但增加站立和体重减轻。另一方面，SKF82958 与美金刚联合给药可防止其以相同剂量单独给药时产生的一些效应。此外，EE 并没有改变吗啡戒断的强度。SE 吗啡戒断组的海马 tPA mRNA 水平低于安慰剂组，接近 EE 吗啡戒断组，而美金刚组或 SKF82958 组的海马 tPA mRNA 水平没有显着变化。这些发现表明，谷氨酸能系统和多巴胺能系统之间的相互作用可能是吗啡依赖性神经生物学的重要组成部分，并且应该进一步研究tPA在这种相互作用中的作用。