Van den Buuse M
Marion Merrell Dow Research Institute, Strasbourg, France.
Eur J Pharmacol. 1993 Oct 19;243(2):169-77. doi: 10.1016/0014-2999(93)90377-t.
The in vivo effects of administration of the putative dopamine D3 receptor agonist 7-hydroxy-N,N-di-n-propylaminotetralin (7-OH-DPAT) were investigated in spontaneously hypertensive rats (SHR) and normotensive wistar-Kyoto controls (WKY). The i.p. injection of 7-OH-DPAT induced hyperactivity in WKY at 10 mg/kg, but only an inhibition of exploratory locomotor activity was observed in SHR at 1 mg/kg. In WKY and SHR with unilateral lesions of the nigrostriatal system, s.c. injection of 0.01-1 mg/kg of 7-OH-DPAT induced dose-dependent contralateral turning behaviour. This response was more pronounced in SHR than in WKY. The s.c. injection of 0.03, but not of 0.01 or 0.1 mg/kg, of 7-OH-DPAT induced yawning in WKY and SHR. The i.v. injection of 0.1 or 1 mg/kg of 7-OH-DPAT induced an immediate rise in blood pressure in both WKY and SHR. Pretreatment with the dopamine receptor antagonist haloperidol partially prevented this pressor response and, in addition, unmasked a late fall in blood pressure in SHR. The s.c. injection of 1 mg/kg of 7-OH-DPAT induced a decrease in body temperature, which was more pronounced in SHR than in WKY. This effect could be inhibited by pretreatment with haloperidol, but a residual hypothermia remained in SHR. These results suggest that 7-OH-DPAT induces a variety of effects in vivo, many of which may be mediated by dopamine D2 receptors or non-dopaminergic receptors. Thus, more selective dopamine D3 receptor agonists or -antagonists are needed to further explore the role of dopamine D3 receptors in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
在自发性高血压大鼠(SHR)和正常血压的Wistar-Kyoto对照大鼠(WKY)中研究了假定的多巴胺D3受体激动剂7-羟基-N,N-二正丙基氨基四氢萘(7-OH-DPAT)给药的体内效应。腹腔注射7-OH-DPAT在WKY中以10mg/kg剂量诱导多动,但在SHR中仅在1mg/kg剂量时观察到探索性运动活动受到抑制。在黑质纹状体系统单侧损伤的WKY和SHR中,皮下注射0.01-1mg/kg的7-OH-DPAT诱导剂量依赖性的对侧转向行为。这种反应在SHR中比在WKY中更明显。皮下注射0.03mg/kg(而非0.01或0.1mg/kg)的7-OH-DPAT在WKY和SHR中诱导打哈欠。静脉注射0.1或1mg/kg的7-OH-DPAT在WKY和SHR中均诱导血压立即升高。用多巴胺受体拮抗剂氟哌啶醇预处理可部分预防这种升压反应,此外,还可揭示SHR中血压的后期下降。皮下注射1mg/kg的7-OH-DPAT诱导体温降低,这在SHR中比在WKY中更明显。这种效应可被氟哌啶醇预处理抑制,但SHR中仍残留体温过低。这些结果表明,7-OH-DPAT在体内诱导多种效应,其中许多可能由多巴胺D2受体或非多巴胺能受体介导。因此,需要更具选择性的多巴胺D3受体激动剂或拮抗剂来进一步探索多巴胺D3受体在体内的作用。(摘要截短为250字)