Li Su-Min, Collins Gregory T, Paul Noel M, Grundt Peter, Newman Amy H, Xu Ming, Grandy David K, Woods James H, Katz Jonathan L
Psychobiology Section, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224, USA.
Behav Pharmacol. 2010 May;21(3):171-81. doi: 10.1097/FBP.0b013e32833a5c68.
Dopaminergic (DA) agonist-induced yawning in rats seems to be mediated by DA D3 receptors, and low doses of several DA agonists decrease locomotor activity, an effect attributed to presynaptic D2 receptors. Effects of several DA agonists on yawning and locomotor activity were examined in rats and mice. Yawning was reliably produced in rats, and by the cholinergic agonist, physostigmine, in both the species. However, DA agonists were ineffective in producing yawning in Swiss-Webster or DA D2R and DA D3R knockout or wild-type mice. The drugs significantly decreased locomotor activity in rats at one or two low doses, with activity returning to control levels at higher doses. In mice, the drugs decreased locomotion across a 1000-10 000-fold range of doses, with activity at control levels (U-91356A) or above control levels [(+/-)-7-hydroxy-2-dipropylaminotetralin HBr, quinpirole] at the highest doses. Low doses of agonists decreased locomotion in all mice except the DA D2R knockout mice, but were not antagonized by DA D2R or D3R antagonists (L-741 626, BP 897, or PG01037). Yawning does not provide a selective in-vivo indicator of DA D3R agonist activity in mice. Decreases in mouse locomotor activity by the DA agonists seem to be mediated by D2 DA receptors.
多巴胺能(DA)激动剂诱发大鼠打哈欠似乎是由DA D3受体介导的,而几种低剂量的DA激动剂会降低运动活性,这种效应归因于突触前D2受体。研究了几种DA激动剂对大鼠和小鼠打哈欠及运动活性的影响。在大鼠中能可靠地诱发打哈欠,在这两个物种中,胆碱能激动剂毒扁豆碱也能诱发打哈欠。然而,DA激动剂对瑞士-韦伯斯特小鼠或DA D2R和DA D3R基因敲除或野生型小鼠的打哈欠无效。这些药物在一两个低剂量时能显著降低大鼠的运动活性,而在高剂量时活性恢复到对照水平。在小鼠中,这些药物在1000至10000倍的剂量范围内降低运动,在最高剂量时活性处于对照水平(U-91356A)或高于对照水平[(±)-7-羟基-2-二丙基氨基四氢萘溴化物、喹吡罗]。低剂量的激动剂能降低除DA D2R基因敲除小鼠外的所有小鼠的运动,但不受DA D2R或D3R拮抗剂(L-741626、BP 897或PG01037)的拮抗。打哈欠并不是小鼠体内DA D3R激动剂活性的选择性指标。DA激动剂降低小鼠运动活性似乎是由DAT2受体介导的。