James T A, Starr M S
Br J Pharmacol. 1979 Mar;65(3):423-9. doi: 10.1111/j.1476-5381.1979.tb07846.x.
1 Behavioural and biochemical effects of substance P (SP, 1 to 10 mug) administered in a small volume to discrete areas of the rat's brain were studied by means of a refined microinjection technique.2 SP injected unilaterally into the zona reticulata of the substantia nigra elicited dose-dependent contraversive circling and an increase in dopamine turnover in the ipsilateral striatum. SP applied to the zona compacta or zona lateralis, or to the medial lemniscus, evoked ipsiversive turning with a fall in dopamine turnover and a rise in 5-hydroxytryptamine (5-HT) turnover in the corresponding striatum.3 In both cases the onset of turning was immediate, reached a peak at about 5 min and lasted for 10 min. Both types of behaviour were blocked by haloperidol and exaggerated by nialamide.4 Unilateral injections of SP given into the crus cerebri, zona incerta, caudate nucleus, putamen or globus pallidus did not modify the animal's behaviour.5 In rats pretreated with apomorphine or amphetamine, SP induced contraversive circling which was followed by locomotion in the opposite direction.6 Turning responses to a second dose of SP were diminished at 3 h and reproducible at 24 h after the first injection.7 Bacitracin (50 ng) injected into the zona reticulata caused ipsiversive turning. Larger intranigral doses of bacitracin (10 mug), as with intracisternal SP (10 mug), evoked ;barrel rotation'.8 No changes in the free concentrations of aspartate, glutamate, gamma-aminobutyric acid, glycine or alanine were detected in any brain region following an intracisternal injection of 10 mug SP, although glutamine levels were elevated throughout the brain 30 to 60 min later.
采用改良的微量注射技术,研究了向大鼠脑的离散区域微量注射P物质(SP,1至10微克)的行为学和生物化学效应。
单侧注射到黑质网状带的SP引起剂量依赖性的向对侧旋转,并使同侧纹状体中的多巴胺周转率增加。注射到致密带、外侧带或内侧丘系的SP,引起向同侧旋转,相应纹状体中的多巴胺周转率下降,5-羟色胺(5-HT)周转率上升。
在这两种情况下,旋转均立即开始,约5分钟达到峰值,并持续10分钟。两种行为均被氟哌啶醇阻断,被尼亚酰胺增强。
向大脑脚、未定带、尾状核、壳核或苍白球单侧注射SP不改变动物行为。
在预先用阿扑吗啡或苯丙胺处理的大鼠中,SP诱导向对侧旋转,随后向相反方向运动。
对第二剂SP的旋转反应在第一次注射后3小时减弱,24小时可重现。
注射到网状带的杆菌肽(50纳克)引起向同侧旋转。较大剂量的脑内注射杆菌肽(10微克),与脑池内注射SP(10微克)一样,引起“桶状旋转”。
脑池内注射10微克SP后,在任何脑区均未检测到天冬氨酸、谷氨酸、γ-氨基丁酸、甘氨酸或丙氨酸的游离浓度变化,尽管30至60分钟后全脑谷氨酰胺水平升高。