Blakley Gregory G, Pohorecky Larissa A, Benjamin Daniel
Neuropharmacology Laboratory, Rutgers University Center of Alcohol Studies, 607 Allison Road, Piscataway, NJ 08855, USA.
Psychopharmacology (Berl). 2004 Feb;171(4):421-8. doi: 10.1007/s00213-003-1597-5. Epub 2003 Nov 18.
Compared with the use of classic receptor ligands, antisense oligonucleotides (ASO) targeted at specific central nervous system receptors are an effective alternative in experiments designed to examine the behavioral role of such systems.
The nociception/orphaninFQ (N/OFQ) system has been implicated in mediating endocrine function, feeding, stress, pain, anxiety, and the rewarding effects of drugs of abuse. The objective of the current study was to examine whether long-term ASO-induced downregulation of N/OFQ's receptor (NOP) produced changes in endocrine, anxiety, nociception and ethanol's (EtOH's) locomotor activating properties.
Male Long Evans rats were implanted with osmotic mini-pumps containing ASO for the NOP receptor. ASO was chronically infused for 26 days and, during this time, multiple behavioral and physiological measurements were conducted.
ASO infusion significantly reduced expression of the NOP receptor in brain, confirmed by significant reductions of OFQ-stimulated [(35)S]-GTPgammaS binding in the paraventricular nucleus, prefrontal cortex, and septum. Behavioral changes were observed in ASO-treated animals including higher body temperature, increased water intake, decreased corticosterone (CORT) levels, decreased grooming in the open field, increased tail-flick latency, shorter durations on the open arms of the elevated plus maze, and heightened locomotor activity following EtOH.
These behavioral, physiological and endocrine changes are relatively consistent with previous findings with agonists and antagonists for the NOP receptor and, taken together, suggest that ASO-induced downregulation of the NOP receptor is an effective method for studying the N/OFQ system.
与使用经典受体配体相比，针对特定中枢神经系统受体的反义寡核苷酸（ASO）在旨在研究此类系统行为作用的实验中是一种有效的替代方法。
伤害感受/孤啡肽FQ（N/OFQ）系统已被认为参与介导内分泌功能、进食、应激、疼痛、焦虑以及滥用药物的奖赏效应。本研究的目的是检验长期ASO诱导的N/OFQ受体（NOP）下调是否会导致内分泌、焦虑、伤害感受以及乙醇（EtOH）运动激活特性的改变。
给雄性Long Evans大鼠植入含有针对NOP受体的ASO的渗透微型泵。ASO持续输注26天，在此期间进行多项行为和生理测量。
ASO输注显著降低了脑中NOP受体的表达，这通过室旁核、前额叶皮质和隔区中OFQ刺激的[（35）S]-GTPγS结合的显著减少得到证实。在接受ASO治疗的动物中观察到行为变化，包括体温升高、饮水量增加、皮质酮（CORT）水平降低、旷场实验中梳理行为减少、甩尾潜伏期延长、高架十字迷宫开放臂上停留时间缩短以及EtOH给药后运动活性增强。
这些行为、生理和内分泌变化与先前使用NOP受体激动剂和拮抗剂的研究结果相对一致，综合来看，表明ASO诱导的NOP受体下调是研究N/OFQ系统的有效方法。
