Daws L C, Lopez R, Frazer A
Department of Pharmacology, University of Texas Health Science Center, San Antonio, Texas, USA.
Neuropsychopharmacology. 1998 Oct;19(4):300-13. doi: 10.1016/S0893-133X(98)00016-5.
Chronic treatment of rats with a variety of antidepressants results in the down-regulation of beta-1-adrenoceptors in the amygdaloid nuclei. The present study sought to determine if this specific neurochemical effect caused an alteration in inhibitory avoidance conditioning, a behavior considered to be mediated by beta-adrenoceptors in the amygdala. Rats treated chronically with either desipramine (DMI) or phenelzine (PHEN), which down-regulate beta-1-adrenoceptors in the amygdala, or fluoxetine (FLUOX), which does not do this, did not exhibit a deficit in the retention of the inhibitory avoidance task. However, when scopolamine was given prior to acquisition of the task in a dose that, by itself, did not affect retention, DMI- and PHEN-treated rats showed a marked deficit in retention. This effect was also observed after acute administration of these drugs, although they did not down-regulate amygdaloid beta-1-adrenoceptors at this time. It seems that the ability of these antidepressants to potentiate the amnesic effect of scopolamine is unrelated to their effect on beta-1-adrenoceptor number in the amygdala and that the extent of the antidepressant-induced amygdaloid beta-1-adrenoceptor down-regulation is not sufficient, by itself, to cause a deficit in an inhibitory avoidance task.
用多种抗抑郁药对大鼠进行长期治疗会导致杏仁核中β-1-肾上腺素能受体下调。本研究旨在确定这种特定的神经化学效应是否会导致抑制性回避条件反射发生改变，抑制性回避条件反射是一种被认为由杏仁核中的β-肾上腺素能受体介导的行为。长期用去甲丙咪嗪（DMI）或苯乙肼（PHEN）治疗的大鼠，这两种药物会下调杏仁核中的β-1-肾上腺素能受体，或用氟西汀（FLUOX）治疗的大鼠，氟西汀不会下调该受体，这些大鼠在抑制性回避任务的记忆保持方面均未表现出缺陷。然而，当在任务习得前给予东莨菪碱，其剂量本身并不影响记忆保持时，DMI和PHEN治疗的大鼠在记忆保持方面表现出明显缺陷。在急性给予这些药物后也观察到了这种效应，尽管此时它们并未下调杏仁核β-1-肾上腺素能受体。似乎这些抗抑郁药增强东莨菪碱失忆效应的能力与其对杏仁核中β-1-肾上腺素能受体数量的影响无关，而且抗抑郁药诱导的杏仁核β-1-肾上腺素能受体下调程度本身并不足以导致抑制性回避任务出现缺陷。
