Danysz W, Kostowski W, Kozak W, Hauptmann M
Pol J Pharmacol Pharm. 1986 May-Jun;38(3):285-98.
Three weeks of treatment with desipramine (DMI) and amitriptyline (AMI) reduced the hypothermic action of clonidine in rats. Both electrolytic and 6-hydroxydopamine lesions of the locus coeruleus (LC) and administration of DSP-4 counteracted the reduction of clonidine hypothermia produced by antidepressants. Lesions of the LC and DSP-4 administration also antagonized the anti-immobility action of single doses of DMI but failed to modulate the action of AMI in the forced swim test. Chronic DMI action on the rat immobility was reduced by 6-hydroxydopamine lesions of the LC: other lesions (electrolytic, DSP-4) were ineffective. Electrical stimulation of the LC increased the rat activity in the forced swim paradigm, producing an effect similar to that of antidepressants. The anti-immobility effect of DMI as well as LC stimulation were antagonized by drugs blocking alpha-adrenoceptors (phenoxybenzamine, prazosin) but not by propranolol, a non-selective antagonist of beta-adrenoceptors. On the other hand, the anti-immobility action of AMI was unchanged by all adrenolytics used in that study. The results indicate that the LC system and alpha 1-adrenoceptors play an important role in the antidepressive action of DMI, but not AMI, in the forced swim test.
用去甲丙咪嗪（DMI）和阿米替林（AMI）治疗三周可降低可乐定对大鼠的体温过低作用。蓝斑（LC）的电解损伤和6-羟基多巴胺损伤以及给予DSP-4均可抵消抗抑郁药所产生的可乐定体温过低的降低作用。LC损伤和给予DSP-4也可拮抗单剂量DMI的抗不动作用，但在强迫游泳试验中未能调节AMI的作用。LC的6-羟基多巴胺损伤可降低DMI对大鼠不动的慢性作用：其他损伤（电解损伤、DSP-4）则无效。电刺激LC可增加大鼠在强迫游泳范式中的活动，产生类似于抗抑郁药的效果。DMI的抗不动作用以及LC刺激均被阻断α-肾上腺素能受体的药物（酚苄明、哌唑嗪）所拮抗，但不被β-肾上腺素能受体的非选择性拮抗剂普萘洛尔所拮抗。另一方面，该研究中使用的所有肾上腺素能阻断剂均未改变AMI的抗不动作用。结果表明，在强迫游泳试验中，LC系统和α1-肾上腺素能受体在DMI而非AMI的抗抑郁作用中起重要作用。
