Abstract:
Behavioural sensitization (BS) is characterized by enhanced psychomotor responses to a dose of substance of abuse after prior repeated exposure. We previously reported that BS can be induced by a single injection of morphine in rats, whereas septal nuclei are specifically involved in the development phase of BS. Here, we demonstrated that intra-LS or intra-MS microinjections also incubated BS to a systemic morphine injection in a cross-sensitization fashion, whereas inactivation of either subdivision of septal nuclei (LS: lateral septum; MS: medial septum) can negate this ability of morphine. Then, non-selective (naloxone) and selective (μ-, δ- and κ-)opioid receptor antagonists were directly delivered into LS or MS, respectively, ahead of a morphine microinjection, whereas only μ-opioid receptors in both LS and MS play indispensable roles in mediating the BS development. Finally, there was a pronounced elevation in the levels of the monoamines (i.e. dopamine, homovanillic acid, 5-hydroxytryptamine and 5-hydroxyindoleacetic acid) in the septum, 8 h after a morphine injection detected with a HPLC-ECD method, suggesting that dopaminergi and serotoninergic systems are implicated in the BS formation. Our studies demonstrated that septal nuclei critically participate in the BS development. Essentially, μ- instead of δ- or κ-opioid receptors in LS and MS mediate sensitization to opiates.
摘要:
行为致敏(BS)的特征是在先前重复暴露后对一定剂量的滥用物质的精神运动反应增强。我们以前报道过,大鼠单次注射吗啡可以诱发BS,而间隔核特别参与BS的发展阶段。这里,我们证明了LS内或MS内微量注射也以交叉致敏方式将BS孵育到全身吗啡注射中,而间隔核的任一细分(LS:外侧间隔;MS:内侧间隔)的失活可以抵消吗啡的这种能力。然后,非选择性(纳洛酮)和选择性(μ-,δ-和κ-)阿片受体拮抗剂直接递送至LS或MS,分别,在吗啡显微注射之前,而LS和MS中只有μ阿片受体在介导BS的发展中起着不可或缺的作用。最后,单胺(即多巴胺,高香草酸,隔膜中的5-羟色胺和5-羟基吲哚乙酸),用HPLC-ECD方法检测吗啡注射后8小时,表明多巴胺和5-羟色胺能系统与BS的形成有关。我们的研究表明,间隔核关键参与BS的发展。本质上,LS和MS中的μ-而不是δ-或κ-阿片受体介导对阿片类药物的敏化。