Kalivas P W, Burgess S K, Nemeroff C B, Prange A J
Neuroscience. 1983 Mar;8(3):495-505. doi: 10.1016/0306-4522(83)90195-1.
The ventral tegmental area of the rat brain has been shown to possess high densities of neurotensin- and dopamine-containing neuronal perikarya. We recently demonstrated that microinjection of neurotensin into the ventral tegmental area produces behavioral hyperactivity similar to amphetamine-induced increase in exploratory behaviors, but lacking stereotypies. In this study, we report that the threshold dose for neurotensin-induced hyperactivity is 0.10-0.25 micrograms neurotensin/side. Either intracerebroventricular injection of haloperidol (5.0 micrograms/lateral ventricle) or destruction of the mesolimbic dopamine system by 6-hydroxydopamine abolishes the behavioral hyperactivity produced by intraventral tegmental injection of neurotensin (2.5 micrograms/side). Using high pressure liquid chromatography with electrochemical detection, we show that neurotensin injection into the ventral tegmental area increases the concentration of dopamine metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid in the nucleus accumbens and olfactory tubercles, but not in the striatum. This effect is especially profound in the nucleus accumbens where the threshold dose is less than 0.025 micrograms/side. The ratio of 3,4-dihydroxyphenylacetic acid to dopamine increased in the nucleus accumbens and olfactory tubercles in a dose-dependent fashion (0.025 microgram-2.50 micrograms/side). Neurotensin-induced behavioral hyperactivity correlates positively with neurotensin-induced changes in the ratio of 3,4-dihydroxyphenylacetic acid to dopamine. This study indicates that neurotensin acts in the ventral tegmental area to activate the mesolimbic dopamine system. Further, this activation produces behavioral hyperactivity characterized by an increase in exploratory behaviors. The fact that both immunoreactive neurotensin and neurotensin receptors are found in high concentration in the ventral tegmental area supports the possible physiological significance of this peptide-catecholamine interaction.
大鼠脑的腹侧被盖区已被证明含有高密度的含神经降压素和多巴胺的神经元胞体。我们最近证明，向腹侧被盖区微量注射神经降压素会产生行为多动，类似于苯丙胺诱导的探索行为增加，但没有刻板行为。在本研究中，我们报告神经降压素诱导多动的阈剂量为0.10 - 0.25微克神经降压素/侧。脑室内注射氟哌啶醇（5.0微克/侧脑室）或用6 - 羟基多巴胺破坏中脑边缘多巴胺系统，均可消除腹侧被盖区内注射神经降压素（2.5微克/侧）所产生的行为多动。使用高压液相色谱 - 电化学检测，我们发现向腹侧被盖区注射神经降压素会增加伏隔核和嗅结节中多巴胺代谢产物3,4 - 二羟基苯乙酸和高香草酸的浓度，但纹状体中没有增加。这种效应在伏隔核中尤为显著，其阈剂量小于0.025微克/侧。伏隔核和嗅结节中3,4 - 二羟基苯乙酸与多巴胺的比值呈剂量依赖性增加（0.025微克 - 2.50微克/侧）。神经降压素诱导的行为多动与神经降压素诱导的3,4 - 二羟基苯乙酸与多巴胺比值变化呈正相关。本研究表明，神经降压素在腹侧被盖区起作用以激活中脑边缘多巴胺系统。此外，这种激活产生以探索行为增加为特征的行为多动。腹侧被盖区中免疫反应性神经降压素和神经降压素受体均高浓度存在这一事实支持了这种肽 - 儿茶酚胺相互作用可能的生理意义。
