Lutfy K, Do T, Maidment N T
Department of Psychiatry and Biobehavioral Sciences, Neuropsychiatric Institute, University of California, Los Angeles 90024, USA.
Psychopharmacology (Berl). 2001 Feb;154(1):1-7. doi: 10.1007/s002130000609.
Orphanin FQ (OFQ; also known as nociceptin), the endogenous ligand of the opioid receptor-like receptor, injected intracerebroventricularly (i.c.v.) decreases basal motor activity and basal extracellular levels of dopamine (DA) in the nucleus accumbens (Nuc Acc) in rats.
The present study was designed to determine if OFQ similarly attenuates cocaine-induced motor stimulation and to determine if this effect is dependent on attenuation of the increase in extracellular DA.
After a 1-h adaptation period, rats were injected with either artificial cerebrospinal fluid or OFQ (3-30 nmol, i.c.v.) 5 min prior to cocaine (10 mg/kg, i.p.) or apomorphine (3 mg/kg, i.p.) administration and the total distance traveled was measured for a further 1 h. In a separate experiment, changes in extracellular DA were monitored by microdialysis following cocaine and OFQ treatment in anesthetized rats.
OFQ dose-dependently attenuated both basal and cocaine-induced motor stimulation. OFQ (30 nmol, i.c.v.) also attenuated both the basal and the cocaine-induced increase in extracellular DA in the Nuc Acc. OFQ, at the highest dose, also decreased the motor stimulation induced by apomorphine.
Our results suggest that the modulatory effect of OFQ on locomotor activity is not solely due to its inhibitory action on extracellular DA in the Nuc Acc.
孤啡肽（OFQ；也称为痛敏肽），即阿片受体样受体的内源性配体，脑室内注射可降低大鼠的基础运动活性以及伏隔核中多巴胺（DA）的基础细胞外水平。
本研究旨在确定OFQ是否同样减弱可卡因诱导的运动兴奋，并确定这种作用是否依赖于细胞外DA增加的减弱。
在1小时适应期后，大鼠在给予可卡因（10mg/kg，腹腔注射）或阿扑吗啡（3mg/kg，腹腔注射）前5分钟，脑室内注射人工脑脊液或OFQ（3-30nmol），并在接下来的1小时内测量总行进距离。在另一项实验中，在麻醉大鼠中，经可卡因和OFQ处理后，通过微透析监测细胞外DA的变化。
OFQ剂量依赖性地减弱基础和可卡因诱导的运动兴奋。脑室内注射30nmol OFQ也减弱了伏隔核中基础和可卡因诱导的细胞外DA增加。最高剂量的OFQ也降低了阿扑吗啡诱导的运动兴奋。
我们的结果表明，OFQ对运动活性的调节作用并非仅仅归因于其对伏隔核中细胞外DA的抑制作用。
