Vitale Giovanni, Arletti Rossana, Ruggieri Valentina, Cifani Carlo, Massi Maurizio
Department of Biomedical Sciences, Section of Pharmacology, University of Modena and Reggio Emilia, I-41100 Modena, Italy.
Peptides. 2006 Sep;27(9):2193-200. doi: 10.1016/j.peptides.2006.04.003. Epub 2006 May 26.
Different reports suggest that nociceptin/orphanin FQ (N/OFQ) may have either anxiolytic- or anxiogenic-like effect in rodents. Since N/OFQ elicits hypolocomotion, which undergoes rapid tolerance, and hypolocomotion may be associated to emotional consequences, the present study was designed to investigate the effect of N/OFQ on anxiety after development of tolerance to its hypolocomotor effect. The effect of single or double intracerebroventricular (i.c.v.) injection of N/OFQ was evaluated on anxiety-related behaviors in rats, in the elevated plus maze (EPM) and conditioned defensive burying (CDB) tests. After single administration, N/OFQ displayed an anxiogenic-like pattern of response on the elevated plus maze but hypolocomotion was also observed. Conversely, in the CDB test, N/OFQ induced a clear-cut anxiolytic pattern. To produce tolerance to N/OFQ-induced hypolocomotion the peptide was administered by two i.c.v. injections separated by 120 min; in these conditions it decreased the expression of anxiety-related behaviors in both tests without affecting locomotor activity. The nociceptin/orphanin FQ peptide (NOP) receptor antagonist UFP-101 significantly reduced the effects of N/OFQ to control values in either tests. Corticosterone levels were significantly increased after a single N/OFQ administration (not in a dose-dependent manner) but this increase did not reach significance after double administration (1 nmol/rat). Our results support the idea that N/OFQ may act as an anxiolytic-like agent in the rat; the apparent anxiogenic-like effect observed following its single administration in the EPM may be consequent to its effect on locomotion.
不同的报告表明，痛敏肽/孤啡肽FQ（N/OFQ）在啮齿动物中可能具有抗焦虑或促焦虑样作用。由于N/OFQ会引起运动减少，且这种运动减少会迅速产生耐受性，并且运动减少可能与情绪后果相关，因此本研究旨在探讨在对其运动减少作用产生耐受性后，N/OFQ对焦虑的影响。通过在高架十字迷宫（EPM）和条件性防御性埋洞（CDB）试验中，评估单次或两次脑室内（i.c.v.）注射N/OFQ对大鼠焦虑相关行为的影响。单次给药后，N/OFQ在高架十字迷宫上呈现出促焦虑样的反应模式，但也观察到了运动减少。相反，在CDB试验中，N/OFQ诱导出明显的抗焦虑模式。为了使动物对N/OFQ诱导的运动减少产生耐受性，通过两次间隔120分钟的脑室内注射给予该肽；在这些条件下，它在两项试验中均降低了焦虑相关行为的表现，而不影响运动活性。痛敏肽/孤啡肽FQ肽（NOP）受体拮抗剂UFP - 101在任一试验中均显著将N/OFQ的作用降低至对照值。单次给予N/OFQ后，皮质酮水平显著升高（并非呈剂量依赖性），但两次给药（1 nmol/大鼠）后这种升高未达到显著水平。我们的结果支持N/OFQ可能在大鼠中作为一种抗焦虑样药物起作用的观点；在EPM中单次给药后观察到的明显促焦虑样作用可能是其对运动的影响所致。
