Nikolaev S V, Lebedev A A, Bychkov E R, Oblyapin A V, Dambinova S A, Shabanov P D
Institute of the Human Brain, Russian Academy of Sciences, 12a Academician Pavlov Street, 197376 St. Petersburg, Russia.
Neurosci Behav Physiol. 2004 Sep;34(7):743-6. doi: 10.1023/b:neab.0000036016.65208.27.
In vivo microdialysis was used to study the effects of substance P on dopamine, dihydroxyphenylacetic acid, and homovanillic acid levels in the nucleus accumbens in rats. Each animal received sequential injections of physiological saline, 0.1 microg of substance P, and 1 microg of substance P into the lateral ventricle over three days. Dialysates showed increases in dopamine levels in response to neuropeptide, by 41% for the 0.1 microg dose and 71% for the 1 microg dose. The dynamics of these changes also depended on the concentration of the agent. Administration of 1 microg of substance P gave a peak dopamine level at 50 min; the neurotransmitter level remained significantly elevated 75 min after dosage with substance P. The dopamine level was increased only at 75 min when the 0.1 microg dose of neuropeptide was used. Changes in metabolite levels were also dose-dependent. After the 1 microg dose, the dihydroxyphenylacetic acid level increased by 28%, while the 0.1 microg dose produced no significant change in the level of this metabolite. The homovanillic acid level did not respond to administration of substance P at either dose. These data support the suggestion that the influence of substance P on the internal compensation system is to a significant extent mediated by dopaminergic mechanisms and provides a possible explanation for the effects of the neuropeptide seen in a conditioned place preference reflex.
采用体内微透析技术研究P物质对大鼠伏隔核中多巴胺、二羟基苯乙酸和高香草酸水平的影响。在三天内，每只动物依次接受向侧脑室内注射生理盐水、0.1微克P物质和1微克P物质。透析液显示，对神经肽的反应中多巴胺水平升高，0.1微克剂量时升高41%，1微克剂量时升高71%。这些变化的动态也取决于药物浓度。注射1微克P物质后，多巴胺水平在50分钟时达到峰值；给药后75分钟，神经递质水平仍显著升高。使用0.1微克神经肽剂量时，多巴胺水平仅在75分钟时升高。代谢物水平的变化也是剂量依赖性的。1微克剂量后，二羟基苯乙酸水平升高了28%，而0.1微克剂量对该代谢物水平没有显著影响。两种剂量的P物质给药后，高香草酸水平均无反应。这些数据支持以下观点，即P物质对内部补偿系统的影响在很大程度上是由多巴胺能机制介导的，并为在条件性位置偏好反射中观察到的神经肽效应提供了一种可能的解释。
