Smittkamp Susan, Spalding Heather, Zhang Hongyu, Stanford John A
Department of Molecular & Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Blvd., Mailstop 3051, Kansas City, KS, 66160, USA.
Psychopharmacology (Berl). 2014 Dec;231(24):4695-701. doi: 10.1007/s00213-014-3620-4. Epub 2014 Jun 13.
Orolingual motor deficits, such as dysarthria and dysphagia, contribute to increased morbidity and mortality in the elderly. In preclinical studies, we and others have reported age-related decreases in tongue motility in both F344 and F344/BN rats. The fact that these deficits are associated with nigrostriatal dopamine (DA), tissue measures suggest that increasing dopamine function might normalize tongue motility.
The purpose of the current study was to determine whether two indirect dopamine agonists with locomotor-enhancing effects, d-amphetamine (amphetamine; 1 and 2 mg/kg) and GBR-12909 (5, 10, and 20 mg/kg), can improve tongue motility in aged F344/BN rats.
Young (6 months) and aged (30 months) F344/BN rats licked water from an isometric force disc so that tongue motility (licks/second) and tongue force could be measured as a function of age and drug dose.
Consistent with our previous studies, tongue force was greater and tongue motility was lower in the aged group. Tongue motility was increased by amphetamine but not by GBR-12909. Amphetamine decreased peak tongue force, primarily in the young group. GBR-12909 did not affect tongue force. GBR-12909 increased the number of licks/session in the young group but not in the aged group, while amphetamine increased this measure in both groups.
These results demonstrate differential effects of these drugs on orolingual motor function and suggest that blocking DA uptake is insufficient to increase tongue motility in aging.
口面部运动功能障碍,如构音障碍和吞咽困难,会导致老年人发病率和死亡率上升。在临床前研究中,我们和其他研究人员报告了F344和F344/BN大鼠舌运动能力随年龄增长而下降。这些功能障碍与黑质纹状体多巴胺(DA)有关,组织测量结果表明,增强多巴胺功能可能使舌运动能力恢复正常。
本研究旨在确定两种具有运动增强作用的间接多巴胺激动剂,即右旋苯丙胺(苯丙胺;1和2mg/kg)和GBR-12909(5、10和20mg/kg),是否能改善老年F344/BN大鼠的舌运动能力。
年轻(6个月)和老年(30个月)F344/BN大鼠从一个等距力盘舔水,这样就可以根据年龄和药物剂量测量舌运动能力(舔/秒)和舌力。
与我们之前的研究一致,老年组的舌力更大,舌运动能力更低。苯丙胺可增加舌运动能力,但GBR-12909不能。苯丙胺降低了舌力峰值,主要是在年轻组。GBR-12909不影响舌力。GBR-12909增加了年轻组的每次舔舐次数,但老年组没有增加,而苯丙胺在两组中均增加了这一指标。
这些结果表明这些药物对口面部运动功能有不同影响,并表明阻断多巴胺摄取不足以增加衰老过程中的舌运动能力。