Poltyrev Tatyana, Weinstock Marta
Department of Pharmacology, School of Pharmacy, Hebrew University Medical Centre, Ein Kerem, 91120 Jerusalem, Israel.
Psychopharmacology (Berl). 2004 Jan;171(3):270-6. doi: 10.1007/s00213-003-1577-9. Epub 2003 Sep 4.
The study determined whether oral administration of amitriptyline for 6 weeks from before puberty to prenatally stressed (PS) male and female rats could prevent hyperanxiety in adulthood.
Sprague-Dawley (12) rat dams were stressed by restraint in cylinders thrice daily for 45 min during the last week of pregnancy. Their offspring and those from unstressed dams (12) were given amitriptyline (4.5 mg/kg per day) in the drinking water between 4 and 10 weeks of age. Behaviour was assessed in the elevated plus maze (EPM) in week 10 in group 1 while still receiving the drug; in group 2, 2 weeks after stopping the drug, and in group 3, as in group 2, but after prior exposure to an open field (OF).
When tested while receiving the drug, no clear anxiolytic effect was seen in PS rats, and anxiety was actually increased in control rats, as indicated by the greater amount of time in closed arms of the EPM. Significant anxiolytic effects of amitriptyline (increase in time in open arms of EPM) were seen 2 weeks after stopping the drug in PS females. It could only be demonstrated in PS males after their anxiety in the EPM had been increased as a result of prior exposure to the open field.
Chronic early treatment with amitriptyline can prevent the development of hyperanxiety in PS rats in adulthood. This effect is only detectable after cessation of drug treatment. The anxiolytic effect is more readily detected in females.
本研究旨在确定从青春期前至产前应激（PS）的雄性和雌性大鼠口服阿米替林6周是否能预防成年后的高度焦虑。
12只Sprague-Dawley大鼠母鼠在怀孕最后一周每天被限制在圆筒中三次，每次45分钟，造成应激。它们的后代以及未受应激母鼠的后代（各12只）在4至10周龄时通过饮用水给予阿米替林（每天4.5毫克/千克）。第1组在第10周仍接受药物治疗时，在高架十字迷宫（EPM）中评估行为；第2组在停药2周后评估；第3组与第2组相同，但在先前暴露于旷场（OF）之后评估。
在接受药物测试时，PS大鼠未观察到明显的抗焦虑作用，而对照大鼠的焦虑实际上增加了，如EPM封闭臂中停留时间更长所示。停药2周后，阿米替林对PS雌性大鼠有显著的抗焦虑作用（EPM开放臂停留时间增加）。只有在PS雄性大鼠因先前暴露于旷场而使EPM中的焦虑增加后，才能证明该作用。
早期长期用阿米替林治疗可预防PS大鼠成年后高度焦虑的发展。这种作用只有在停药后才能检测到。抗焦虑作用在雌性中更容易检测到。
