Grupp L A, Harding S
Primary Mechanisms Department, Addiction Research Foundation of Ontario, Toronto, Canada.
Pharmacol Biochem Behav. 1995 Aug;51(4):593-9. doi: 10.1016/0091-3057(94)00380-2.
Subcutaneous injections of angiotensin (ANG) II or III in the periphery reduce alcohol intake and raise water intake. These peptides do not cross the blood-brain barrier and cannot reach the angiotensin receptor-rich sites surrounding the lateral and third ventricles. To examine the effect on alcohol intake of ANG II and III at these ventricular sites, groups of rats were first trained to drink alcohol using a limited access procedure, then surgically prepared with chronic indwelling lateral or third ventricular cannulae, and then reoffered daily 40-min access to alcohol. Neither ANG II (25-200 ng) nor ANG III (25-100 ng) had any effect on alcohol consumption at either of the two ventricular sites. Water consumption was significantly enhanced by both peptides at both sites and could be attenuated by prior treatment with the ANG II antagonist Sar1Thr8-ANG II. The SC administration of ANG II was able to produce a significant reduction in alcohol drinking. These findings demonstrate that ICV administered ANG II or ANG III do not modulate alcohol drinking and that changes in alcohol intake do not result from the thirst promoted by ANG II. Sites in the periphery may be more involved in the interaction between angiotensin and alcohol consumption.
在外周皮下注射血管紧张素(ANG)II 或 III 可减少酒精摄入量并增加水摄入量。这些肽不能穿过血脑屏障,无法到达侧脑室和第三脑室周围富含血管紧张素受体的部位。为了研究在这些脑室部位 ANG II 和 III 对酒精摄入的影响,首先使用限时获取程序对大鼠进行训练使其饮用酒精,然后通过手术植入慢性留置的侧脑室或第三脑室套管,之后每天再给予大鼠 40 分钟获取酒精的机会。在两个脑室部位,ANG II(25 - 200 纳克)和 ANG III(25 - 100 纳克)对酒精消耗均无任何影响。两种肽在两个部位均显著增加了水的消耗量,并且这种增加可被 ANG II 拮抗剂 Sar1Thr8 - ANG II 的预先处理所减弱。皮下注射 ANG II 能够显著减少酒精饮用量。这些发现表明,脑室内注射 ANG II 或 ANG III 不会调节酒精饮用,并且酒精摄入量的变化并非由 ANG II 引发的口渴所致。外周部位可能在血管紧张素与酒精消耗之间的相互作用中发挥更重要的作用。