Rupniak N M, Schaffer L, Siegl P, Iversen S D
Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, UK.
Neuropeptides. 1993 Aug;25(2):115-9. doi: 10.1016/0143-4179(93)90090-w.
We examined the ability of intravenous (i.v.) challenge with pentagastrin to induce behavioural and cardiovascular effects consistent with panic attack in conscious rhesus monkeys. For behavioural evaluation, 4 naive male rhesus monkeys familiar with minimal manual restraint necessary for drug administration received a rapid i.v. bolus of pentagastrin (4, 8 or 16 micrograms/kg) or water on four separate occasions according to a randomised cross-over design. Behaviour was rated by a blind observer continuously during, and for the first 5 min immediately following i.v. injections while the monkey sat on the handler's lap, and then for a further 25 min in an individual observation cage. In separate experiments, the ability of pentagastrin to alter cardiovascular parameters which may accompany panic or anxiety (elevated heart rate and blood pressure) was explored. For cardiovascular studies, 8 male or female rhesus monkeys with femoral artery catheters were chair restrained and received a bolus injection of pentagastrin (4, 8 or 16 micrograms/kg) or saline into the saphenous vein at 30 min intervals. Blood pressure and heart rate were monitored continuously using a Statham Gould pressure transducer. Pentagastrin induced no consistent behavioural or cardiovascular changes. Similar pilot studies using CCK4 also failed to reveal such effects. We conclude that CCK-induced panic-like effects may not be demonstrable following challenge with pentagastrin under laboratory conditions in rhesus monkeys.
我们研究了静脉注射五肽胃泌素能否在清醒的恒河猴身上诱发与惊恐发作相符的行为和心血管效应。为了进行行为评估,4只对药物注射所需的最小程度手动约束熟悉的未经验证的雄性恒河猴,按照随机交叉设计,在四个不同的场合分别接受快速静脉推注五肽胃泌素(4、8或16微克/千克)或水。在静脉注射期间以及注射后紧接着的前5分钟,当猴子坐在饲养员腿上时,由一位不知情的观察者持续对行为进行评分,然后在单独的观察笼中再持续评分25分钟。在单独的实验中,研究了五肽胃泌素改变可能伴随惊恐或焦虑出现的心血管参数(心率和血压升高)的能力。对于心血管研究,8只带有股动脉导管的雄性或雌性恒河猴被固定在椅子上,并每隔30分钟经隐静脉接受一次五肽胃泌素(4、8或16微克/千克)或生理盐水的推注。使用斯塔瑟姆·古尔德压力传感器持续监测血压和心率。五肽胃泌素未诱发一致的行为或心血管变化。使用CCK4进行的类似初步研究也未能揭示出此类效应。我们得出结论,在恒河猴的实验室条件下,用五肽胃泌素激发后,CCK诱导的类似惊恐的效应可能无法得到证实。