Noel M B, Gratton A
McGill University, Douglas Hospital Research Center, Verdun, Quebec, Canada.
Synapse. 1995 Oct;21(2):110-22. doi: 10.1002/syn.890210204.
Chronoamperometry was used in combination with monoamine-selective electrodes to monitor, in nucleus accumbens (NAcc) and prefrontal cortex (PFC) of freely behaving rats, changes in dopamine (DA)-like electrochemical signals elicited by unilateral ventral tegmental microinjections of the selective mu-opioid receptor agonist D-Ala, N-Me-Phe-Gly-Ol-Enkephalin (DAMGO; 0.01, 0.1, and 1.0 nmol). The results show that DAMGO dose-dependently increased electrochemical signals both in Nacc and PFC within a few minutes of injection. While DAMGO elicited signal increases of comparable amplitudes in both regions, the increases recorded in PFC were significantly longer lasting than those in NAcc; at the highest dose tested (1.0 nmol), DAMGO produced signal increases that lasted (mean +/- sem) 129 +/- 7.3 min in PFC and 96 +/- 12.5 min in NAcc. Pretreatment with the opioid receptor antagonist, naloxone (2 mg/kg, sc), significantly attenuated the peak amplitude and reduced the duration of DAMGO-induced (0.1 nmol) signal increases both in PFC and NAcc. In contrast, pretreatment with apomorphine (50 micrograms/kg, sc), a D1/D2 DA receptor agonist, significantly reduced the duration and the rate of rise of the signal increases in both regions but had little effect on the peak increases in signal. Unilateral ventral tegmental DAMGO administration (0.01, 0.1, and 1.0 nmol) also caused dose-dependent increases in contraversive circling the duration of which approximated that of the signal increases recorded in NAcc. However, differences in the time courses of DAMGO-induced contraversive circling and signal increases in NAcc suggest that the behavioral stimulant effect of ventral tegmental mu-opioid receptor activation may not be mediated exclusively by meso-NAcc DA neurons. The results of this study suggest that enkephalins modulate the activity of meso-PFC DA neurons and that behaviorally relevant activation of mu-opioid receptors in the ventral tegmental area increases DA transmission in PFC to a same, if not to a greater extent as in NAcc. These findings are discussed in relation to evidence indicating that the response of meso-NAcc DA neurons to a variety of stimuli, including drugs of abuse, is indirectly regulated by a DA-sensitive neurons in PFC.
采用计时电流法结合单胺选择性电极，监测自由活动大鼠伏隔核（NAcc）和前额叶皮层（PFC）中，选择性μ-阿片受体激动剂D-丙氨酸、N-甲基苯丙氨酸、甘氨酸-脑啡肽（DAMGO；0.01、0.1和1.0纳摩尔）单侧腹侧被盖区微量注射引发的多巴胺（DA）样电化学信号变化。结果显示，注射后几分钟内，DAMGO在NAcc和PFC中均剂量依赖性地增加电化学信号。虽然DAMGO在两个区域引发的信号增加幅度相当，但PFC中记录到的信号增加持续时间明显长于NAcc；在最高测试剂量（1.0纳摩尔）下，DAMGO在PFC中产生的信号增加持续时间（平均值±标准误）为129±7.3分钟，在NAcc中为96±12.5分钟。用阿片受体拮抗剂纳洛酮（2毫克/千克，皮下注射）预处理，可显著减弱峰值幅度，并缩短PFC和NAcc中DAMGO诱导（0.1纳摩尔）信号增加的持续时间。相比之下，用D1/D2 DA受体激动剂阿扑吗啡（50微克/千克，皮下注射）预处理，可显著缩短两个区域信号增加的持续时间和上升速率，但对信号的峰值增加影响不大。单侧腹侧被盖区注射DAMGO（0.01、0.1和1.0纳摩尔）也会引起剂量依赖性的向对侧旋转增加，其持续时间与NAcc中记录到的信号增加持续时间相近。然而，DAMGO诱导的向对侧旋转和NAcc中信号增加的时间进程差异表明，腹侧被盖区μ-阿片受体激活的行为兴奋作用可能并非仅由中脑-NAcc DA神经元介导。本研究结果表明，脑啡肽调节中脑-PFC DA神经元的活动，腹侧被盖区μ-阿片受体的行为相关激活会增加PFC中的DA传递，即使程度不如NAcc，至少也是相同程度。结合相关证据讨论了这些发现，这些证据表明中脑-NAcc DA神经元对包括滥用药物在内的多种刺激的反应，是由PFC中的DA敏感神经元间接调节的。
