Mogensen Jesper, Svendsen Gitte, Lauritsen Klara Tølbøll, Ermens Petra, Hasman Andreas, Elvertorp Soheyla, Plenge Per, Mellerup Erling, Wörtwein Gitta
Department of Psychology, University of Copenhagen, Amager, Njalsgade 88, DK-2300, Copenhagen S, Denmark.
Pharmacol Biochem Behav. 2003 Aug;76(1):197-212. doi: 10.1016/s0091-3057(03)00220-x.
We investigated effects of 15 daily injections of imipramine (20 mg/kg; in one experiment also 10 and 30 mg/kg). The associative learning types (place learning and object recognition) as well as nonassociative learning (habituation of exploration in an open field and within the object recognition test) were studied. Tests were performed immediately after the final injection (early test) and 24 h after the final injection (late test). The 5-HT(1A), 5-HT(1B/D), 5-HT(2A), beta-adrenergic, D(2) receptors were assayed 24 h after the final injection and the 5-HT(2A) and beta-adrenergic receptors were also measured 60 and 96 h after the final injection. While associative types of learning were impaired in early tests, they remained unaffected in late tests and, while the nonassociative learning (habituation of exploration) remained unaffected in early tests, it was changed in late tests. Measured 24 h after the final injection, imipramine (20 and 30 mg/kg per day) down-regulated the concentration of beta-adrenergic and 5-HT(2A) receptors, while leaving all other measured receptors unaffected. However, only the down-regulation of the 5-HT(2A) receptor outlasted the initial 24-h period after the final injection. On the basis of present and previous results, we interpret the impairment of associative types of learning in early tests as a reflection of anticholinergic effects of imipramine, while the modifications of habituation of exploration in late tests are likely primarily to be mediated by imipramine-provoked regulations of serotonergic receptors.
我们研究了连续15天每天注射丙咪嗪（20毫克/千克；在一项实验中还使用了10毫克/千克和30毫克/千克）的效果。研究了联想学习类型（位置学习和物体识别）以及非联想学习（在开放场地和物体识别测试中的探索习惯化）。在最后一次注射后立即进行测试（早期测试）以及在最后一次注射后24小时进行测试（晚期测试）。在最后一次注射后24小时测定5-羟色胺(1A)、5-羟色胺(1B/D)、5-羟色胺(2A)、β-肾上腺素能、D(2)受体，并且在最后一次注射后60小时和96小时也测量5-羟色胺(2A)和β-肾上腺素能受体。虽然在早期测试中联想学习类型受损，但在晚期测试中它们未受影响，并且，虽然非联想学习（探索习惯化）在早期测试中未受影响，但在晚期测试中发生了变化。在最后一次注射后24小时测量发现，丙咪嗪（每天20毫克/千克和30毫克/千克）下调了β-肾上腺素能和5-羟色胺(2A)受体的浓度，而其他所有测量的受体未受影响。然而，只有5-羟色胺(2A)受体的下调在最后一次注射后的最初24小时之后仍持续存在。根据目前和以前的结果，我们将早期测试中联想学习类型的受损解释为丙咪嗪抗胆碱能作用的反映，而晚期测试中探索习惯化的改变可能主要是由丙咪嗪引起的血清素能受体调节介导的。
