Drago F, Nardo L, Rampello L, Raffaele R
Institute of Pharmacology, University of Catania Medical School, Italy.
Pharmacol Res. 1996 Feb;33(2):135-40. doi: 10.1006/phrs.1996.0020.
Drugs acting as agonists (SKF38393 and quinpirol) or antagonists (SCH23390 and sulpiride) on dopamine receptors were administered at various doses (1, 2 or 4 mg kg-1 day-1) to aged male rats of the Sprague-Dawley strain subjected to labyrinth unilateral lesion. The time course of vestibular compensation was evaluated by recording spontaneous eye nystagmus and by scoring ambulation and rearing with the open field test and motor ability and coordination with the rotorod test. Treatment started 3 days prior to surgery and continued until day 7 after surgery. The vestibular compensation of untreated young male rats was also studied with the same methods. The decline of spontaneous nystagmus in aged animals was slower than that of young rats and was facilitated by the large doses of quinpirol (D2 receptor agonist) and inhibited by sulpiride (D2 receptor antagonist) 4 mg kg-1 day-1, while the other drugs did not affect this parameter. After operation, ambulation and rearing of aged rats increased more slowly as compared to that of young animals. Moreover, motor performance and coordination in aged rats improved less rapidly than those of young controls. Dopamine receptor agonists increased ambulation and improved motor performance and coordination in aged rats, while dopamine receptor antagonists exerted opposite effects. Rearing was not affected by any kind of drug treatment. These results suggest that dopamine neurotransmission plays a role in vestibular compensation process following unilateral labyrinthectomy in aged animals, and this may have clinical relevance in vestibular pathologies of peripheral origin that are associated to brain ageing.
将作用于多巴胺受体的激动剂(SKF38393和喹吡罗)或拮抗剂(SCH23390和舒必利)以不同剂量(1、2或4 mg kg-1 天-1)给予接受迷宫单侧损伤的Sprague-Dawley品系老年雄性大鼠。通过记录自发性眼震、采用旷场试验对行走和竖毛行为进行评分以及采用转棒试验对运动能力和协调性进行评估,来评价前庭代偿的时间进程。治疗在手术前3天开始,并持续至术后第7天。还采用相同方法研究了未治疗的年轻雄性大鼠的前庭代偿情况。老年动物自发性眼震的下降比年轻大鼠慢,大剂量喹吡罗(D2受体激动剂)可促进其下降,而4 mg kg-1 天-1的舒必利(D2受体拮抗剂)则抑制其下降,而其他药物对此参数无影响。术后,与年轻动物相比,老年大鼠的行走和竖毛行为增加得更慢。此外,老年大鼠的运动表现和协调性改善速度也比年轻对照组慢。多巴胺受体激动剂可增加老年大鼠的行走,改善其运动表现和协调性,而多巴胺受体拮抗剂则产生相反的作用。竖毛行为不受任何药物治疗的影响。这些结果表明,多巴胺神经传递在老年动物单侧迷路切除术后的前庭代偿过程中起作用,这可能在外周起源且与脑老化相关的前庭病变中具有临床意义。