Rompré P P, Bauco P, Gratton A
Center for Studies in Behavioral Neurobiology, Concordia University, Montréal, Qué., Canada.
Eur J Pharmacol. 1992 Feb 18;211(3):295-303. doi: 10.1016/0014-2999(92)90384-g.
The effects on brain stimulation reward of neurotensin-(1-13) microinjected at different concentrations (2.5, 5, 10 and 20 micrograms/0.5 microliters) into the ventral mesencephalic region containing mesocorticolimbic dopamine neurons were tested in 12 male rats. Neurotensin lowered the stimulation frequency required to sustain threshold levels of responding for brain stimulation reward, suggesting that this neuropeptide is involved in modulating the activity of dopamine neurons that mediate behaviors motivated by positive reinforces. The magnitude of the facilitatory effect of neurotensin on brain stimulation reward was dependent on the concentration injected and to a significant extent also on whether the peptide was administered in an ascending or a descending order of concentration. The different effects of neurotensin depending on the order of administration may suggest long-lasting effects on the responsiveness of neurotensin receptors in this region after injection of high concentrations of the peptide. Subsequent injection of morphine (2.5-5 micrograms/0.5 microliter) into the same site produced a weaker facilitation of brain stimulation reward than expected, suggesting that local damage after multiple central injections or prior injections of neurotensin itself reduced the responsiveness of dopamine neurons to opiates. Taken together, the results are consistent with data indicating that activation of neurotensin receptors in the ventral mesencephalon stimulates dopamine cell firing and axonal dopamine release in limbic terminal fields and suggest that endogenous neurotensin is involved in the control of behavior motivated by positive reinforcement.
在12只雄性大鼠中，测试了将不同浓度（2.5、5、10和20微克/0.5微升）的神经降压素-（1-13）微量注射到含有中脑皮质边缘多巴胺神经元的腹侧中脑区域对脑刺激奖赏的影响。神经降压素降低了维持脑刺激奖赏反应阈值水平所需的刺激频率，这表明这种神经肽参与调节介导由正向强化驱动的行为的多巴胺神经元的活性。神经降压素对脑刺激奖赏的促进作用大小取决于注射浓度，并且在很大程度上还取决于该肽是以浓度升序还是降序给药。神经降压素根据给药顺序产生的不同作用可能表明，在注射高浓度该肽后，对该区域神经降压素受体的反应性有持久影响。随后在同一部位注射吗啡（2.5 - 5微克/0.5微升）对脑刺激奖赏的促进作用比预期弱，这表明多次中枢注射或先前注射神经降压素本身导致的局部损伤降低了多巴胺神经元对阿片类药物的反应性。综上所述，这些结果与以下数据一致，即腹侧中脑的神经降压素受体激活会刺激多巴胺细胞放电以及边缘终末场的轴突多巴胺释放，并表明内源性神经降压素参与由正向强化驱动的行为控制。
