Klenerova Vera, Krejci Ivan, Sida Pavel, Hlinak Zdenek, Hynie Sixtus
Laboratory of Biochemical Neuropharmacology, Institute of Medical Biochemistry, 1st Faculty of Medicine, Charles University in Prague, Czech Republic.
Neuro Endocrinol Lett. 2010;31(5):622-30.
Carbetocin (CBT), an oxytocin (OXY) analog, was designed to exert prolonged peripheral actions. It has also been proposed as potential therapeutic mean in certain psychiatric disorders where OXY role has been implicated. This study examined the effects of both peptides on behavior of naive and restraint stress exposed rats in the open field (OF) and elevated plus maze (EPM) tests.
Spontaneous behavior in the OF and EPM was measured in Wistar rats after intraperitoneal (i.p.) application of OXY or CBT and/or repeated restraint stress. Behavioral parameters were recorded and subsequently elaborated by an automated activity monitoring system (AnyMaze, Stoelting, U.S.A.). Changes in the total movement distance (TMD) and movement in the center area (CMD) were postulated as indicators of the anxiety level.
OXY (0.05 mg/kg) and CBT (0.3 mg/kg) increased TMD but not CMD 60 min after the i.p. treatment; the increased locomotion/exploration indicate participation of arousal/vigilance. Daily stress exposures for three consecutive days, followed by behavioral tests, reduced locomotion of rats in OF and EPM tests; OXY and CBT partly prevented these effects. Five days after the last stress, rats exhibited an increase of both TMD and CMD in the OF. CBT but not OXY prevented these long-term post-stress changes. In the EPM the stressed rats exhibited an increase in time spent in open arms; CBT accelerated this time development. Similar prevention of stress behavioral sequel in OF were obtained in study when stress and peptides were applied for three consecutive days but behavioral testing was postponed for several days to determine the long-lasting effects. CBT reduced the developed locomotor enhancement (6-11 days post-stress) irrespectively whether injected before or after stress.
Repeated restraint stress exposure produced acute and persisting effects on Wistar rat behavior in the OF and EPM tests. CBT either injected before or after stress practically abolished the developed changes in the mobility parameters. The CBT effectiveness to ameliorate the late post-stress behavioral alteration supports the notion of its therapeutic potential in psychiatric disorders in which the role of OXY has been implicated.
卡贝缩宫素（CBT）是一种缩宫素（OXY）类似物，旨在发挥持久的外周作用。它也被提议作为某些涉及OXY作用的精神疾病的潜在治疗手段。本研究在旷场（OF）和高架十字迷宫（EPM）试验中考察了这两种肽对未处理和经束缚应激处理的大鼠行为的影响。
在Wistar大鼠腹腔注射（i.p.）OXY或CBT和/或重复束缚应激后，测量其在OF和EPM中的自发行为。记录行为参数，随后通过自动活动监测系统（AnyMaze，美国Stoelting公司）进行分析。假定总移动距离（TMD）和中心区域移动（CMD）的变化为焦虑水平的指标。
腹腔注射后60分钟，OXY（0.05mg/kg）和CBT（0.3mg/kg）增加了TMD，但未增加CMD；运动/探索增加表明觉醒/警觉参与其中。连续三天每日应激暴露，随后进行行为测试，降低了大鼠在OF和EPM试验中的运动能力；OXY和CBT部分预防了这些影响。最后一次应激后五天，大鼠在OF中的TMD和CMD均增加。CBT而非OXY预防了这些应激后的长期变化。在EPM中，应激大鼠在开放臂中的停留时间增加；CBT加速了这一变化的发展。当连续三天施加应激和肽，但行为测试推迟数天以确定长期影响时，在OF中也获得了类似的应激行为后遗症预防效果。无论在应激前还是应激后注射，CBT均降低了已出现的运动增强（应激后6 - 11天）。
重复束缚应激暴露对Wistar大鼠在OF和EPM试验中的行为产生了急性和持久的影响。无论在应激前还是应激后注射，CBT几乎消除了已出现的运动参数变化。CBT改善应激后晚期行为改变的有效性支持了其在涉及OXY作用的精神疾病中的治疗潜力的观点。
