Cannizzaro C, Plescia F, Gagliano M, Cannizzaro G, Mantia G, La Barbera M, Provenzano G, Cannizzaro E
Dipartimento di Scienze Farmacologiche, Università di Palermo, V. Vespro 129, 90127 Palermo, Italy.
Behav Brain Res. 2008 Jan 10;186(1):98-106. doi: 10.1016/j.bbr.2007.07.036. Epub 2007 Aug 2.
Serotonin is involved in a wide range of physiological and patho-physiological mechanisms. In particular, 5-HT1A receptors are proposed to mediate stress-adaptation. The aim of this research was to investigate in adolescent rats: first, the consequences of perinatal exposure to 5-metoxytryptamine (5MT), a 5-HT1/5-HT2 serotonergic agonist, on behavioural-stress reactivity in elevated plus maze, open field and forced swim tests; secondly, whether the behavioural effects induced by perinatal exposure to 5MT on open field and forced swim tests were affected by the selective 5-HT1A receptor agonist LY 228729, a compound able to elicit a characteristic set of motor behaviours on these experimental models, and by the co-administration of the selective and silent 5-HT1A antagonist WAY 100635. Results indicate that a single daily injection of 5MT to, pregnant dams from gestational days 12 to 21 (1mg/kg s.c.), and to the pups from postnatal days 2 to 18 (0.5mg kg s.c.), induce in the adolescent rat offspring: an increase in the percentage of entries and time spent on the open arms in the elevated plus maze; a reduction in locomotor activity and rearing frequency, and an increase in the time spent on the central areas in the open field test; a decrease in immobility and an increase in swimming in the forced swim test. Acute administration of LY 228729 (1.5mg/kg s.c.) strongly decreases rearing frequency and increases peripheral activity in the open field test, and decreases immobility and increases swimming in the forced swim test both in perinatally vehicle and 5MT-exposed offspring. Co-administration of WAY 100635 (0.25mg/kg s.c.) abolishes the effects exerted by LY 228729. These results suggest that, in the adolescent rat, perinatal exposure to 5MT enhances the stress-related adaptive behavioural responses, presumably through a predominant action on presynaptic 5-HT1A receptors and does not deteriorate the functional response of 5-HT1A receptors to selective agonist and antagonist compounds.
血清素参与多种生理和病理生理机制。特别是，5-HT1A受体被认为介导应激适应。本研究的目的是在青春期大鼠中探究：第一，围产期暴露于5-甲氧基色胺（5MT），一种5-HT1/5-HT2血清素能激动剂，对高架十字迷宫、旷场和强迫游泳试验中行为应激反应性的影响；第二，围产期暴露于5MT对旷场和强迫游泳试验诱导的行为效应是否受到选择性5-HT1A受体激动剂LY 228729的影响，LY 228729是一种能在这些实验模型上引发一组特征性运动行为的化合物，以及是否受到选择性和无活性5-HT1A拮抗剂WAY 100635的共同给药的影响。结果表明，从妊娠第12天至21天（1mg/kg皮下注射）对怀孕母鼠，以及从出生后第2天至18天（0.5mg/kg皮下注射）对幼崽每天单次注射5MT，会在青春期大鼠后代中诱导：在高架十字迷宫中进入开放臂的百分比和在开放臂上花费的时间增加；在旷场试验中运动活动和竖毛频率降低，以及在中央区域花费的时间增加；在强迫游泳试验中不动时间减少，游泳时间增加。急性给予LY 228729（1.5mg/kg皮下注射）在围产期接受载体和5MT暴露的后代中，均会在旷场试验中强烈降低竖毛频率并增加外周活动，在强迫游泳试验中减少不动时间并增加游泳时间。共同给予WAY 100635（0.25mg/kg皮下注射）可消除LY 228729所产生的效应。这些结果表明，在青春期大鼠中，围产期暴露于5MT可增强与应激相关的适应性行为反应，可能是通过对突触前5-HT1A受体的主要作用，并且不会恶化5-HT1A受体对选择性激动剂和拮抗剂化合物的功能反应。
