Kouvelas Dimitrios, Pourzitaki Chrysa, Papazisis Georgios, Dagklis Themistoklis, Dimou Konstantinos, Kraus Michaela M
Department of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Int J Neuropsychopharmacol. 2008 Nov;11(7):925-34. doi: 10.1017/S1461145708008754. Epub 2008 Apr 14.
Anabolic androgenic steroids (AASs) affect areas of the central nervous system, which are involved in emotional and cognitive responses such as sexuality, anxiety, and memory. In the present study we imitated the abuse of AASs by administering high doses of the AAS nandrolone decanoate (ND) to rats. Thereafter rats were exposed to an elevated plus-maze and an olfactory social memory test to evaluate their anxiety-like and cognitive behaviour. To reveal whether these emotional and cognitive changes evoked by ND were caused via direct activation of androgenic receptors (ARs) in the brain, the AR antagonist flutamide (FL) was administered intracerebroventricularly (i.c.v.). Male rats were randomly divided in four groups, one group received 15 mg/kg ND subcutaneously, once daily for 6 wk (ND group). In the second group, in addition to ND, a daily dose of 5 microg FL was injected i.c.v. also for 6 wk (ND+FL group). The third group of rats received only FL and in the control group the vehicle was injected. The ND group clearly spent more time investigating the open arms in the maze test and recognizing the juvenile during the olfactory social memory test in comparison to the control group. In the ND+FL group rats showed similar emotional behaviour and cognitive ability to that of the control group. Injection of FL alone did not affect either anxiety or memory. These results indicate that repeated, high-dose administration of ND decreases anxiety and impairs memory in rats via direct activation of central ARs.
合成代谢雄激素类固醇(AASs)会影响中枢神经系统中涉及情绪和认知反应的区域,如性行为、焦虑和记忆。在本研究中,我们通过给大鼠高剂量注射AAS癸酸诺龙(ND)来模拟AASs的滥用情况。此后,将大鼠置于高架十字迷宫和嗅觉社交记忆测试中,以评估它们的焦虑样行为和认知行为。为了揭示ND引起的这些情绪和认知变化是否是通过直接激活大脑中的雄激素受体(ARs)所致,将AR拮抗剂氟他胺(FL)脑室内注射(i.c.v.)。雄性大鼠随机分为四组,一组皮下注射15mg/kg ND,每天一次,持续6周(ND组)。第二组除注射ND外,还每天脑室内注射5μg FL,同样持续6周(ND+FL组)。第三组大鼠仅注射FL,对照组注射溶剂。与对照组相比,ND组在迷宫测试中明显花更多时间探索开放臂,在嗅觉社交记忆测试中能更好地识别幼鼠。在ND+FL组中,大鼠表现出与对照组相似的情绪行为和认知能力。单独注射FL对焦虑或记忆均无影响。这些结果表明,重复高剂量注射ND会通过直接激活中枢ARs降低大鼠的焦虑并损害其记忆。