Boix F, Sandor P, Nogueira P J, Huston J P, Schwarting R K
Institute of Physiological Psychology I, University of Düsseldorf, Germany.
Neuroscience. 1995 Feb;64(4):1045-55. doi: 10.1016/0306-4522(94)00425-5.
The activity of the neurotransmitter dopamine in the nucleus accumbens is considered to be an important element in the central processing of reinforcement. Unilateral administration of the neurokinin substance P into the area of the nucleus basalis magnocellularis of rats was found to be reinforcing, as assessed by the conditioned place preference paradigm. Simultaneous in vivo microdialysis showed that administration of substance P into the area of the nucleus basalis magnocellularis could increase extracellular concentrations of dopamine in the contralateral nucleus accumbens. Only those animals in which the administration of substance P induced this increase in dopamine levels acquired place preference. Furthermore, the changes in extracellular dopamine levels after substance P administration had a bimodal time course with an acute increase (to about 160% of baseline) during the first hour after injection, with a low (to 120-130%) and enduring increase occurring thereafter. Interestingly, during this second increase there were indications for positive correlations with the degree of place preference induced by substance P. Further positive correlations with place preference were found in the levels of the serotonergic metabolite 5-hydroxyindoleacetic acid. In contrast to dopamine, these were observed ipsi- and contralateral to the side of substance P administration. By combining the methods of in vivo microdialysis and conditioned place preference it was shown that the reinforcing effect induced by unilateral substance P injection in the nucleus basalis magnocellularis is related to dopaminergic (and possibly serotonergic) mechanisms in the nucleus accumbens.
伏隔核中神经递质多巴胺的活性被认为是强化作用中枢处理过程中的一个重要因素。通过条件性位置偏爱范式评估发现,向大鼠基底大细胞核区域单侧注射神经激肽P物质具有强化作用。同时进行的体内微透析显示,向基底大细胞核区域注射P物质可增加对侧伏隔核中多巴胺的细胞外浓度。只有那些注射P物质后多巴胺水平升高的动物才获得了位置偏爱。此外,注射P物质后细胞外多巴胺水平的变化呈现双峰时间进程,注射后第一小时内急性升高(至基线的约160%),随后出现较低(至120 - 130%)且持续的升高。有趣的是,在这第二次升高期间,有迹象表明与P物质诱导的位置偏爱程度呈正相关。在血清素代谢产物5 - 羟吲哚乙酸水平上也发现了与位置偏爱进一步的正相关。与多巴胺不同,这些在注射P物质一侧的同侧和对侧均有观察到。通过结合体内微透析和条件性位置偏爱方法表明,单侧在基底大细胞核注射P物质所诱导的强化作用与伏隔核中的多巴胺能(可能还有血清素能)机制有关。