Stein E A
Department of Psychiatry, Medical College of Wisconsin, Milwaukee 53226.
Synapse. 1993 Jan;13(1):63-73. doi: 10.1002/syn.890130109.
Intracranial self-stimulation (ICS) is thought to activate neuronal systems involved in processing natural reinforcing agents. Metabolic mapping studies have previously demonstrated a subset of CNS structures specifically engaged by ICS in animals receiving stimulation actively vs. passively. Since opiates are known to enhance ICS behavior and presumably its reinforcing properties, the current study addressed the question of the role of opioid peptides as mediators of ICS. Rats were trained on a fixed ration (FR) 20 schedule of responding maintained by ICS. Following response stabilization, rats were assigned either to an active or a corresponding yoked stimulation group at 1 of 2 schedules of reinforcement (i.e., FR1-YFR1, FR20-YFR20, or sedentary control), and opioid peptide release was inferred from in vivo receptor occupancy. Autoradiographic analyses identified 3 groups of structures. Treatment-induced alterations in occupancy were seen in the medial dorsal nucleus of the thalamus, basolateral amygdala, ventral pallidum, medial habenula, dorsal raphe, posterior hypothalamus, substantia nigra pars compacta, agranular preinsular cortex, and zona incerta. Depending upon the structure, peptide release was dependent upon stimulus contingency (active vs. yoked) and/or schedule (FR1 vs. FR20). Evidence for ICS-induced inhibition of peptide release was found in the habenula and preinsular cortex. Nine additional structures, all components of, or receiving projections from, the limbic system, revealed complex interactions between ICS treatment and the electrode side. Finally, a widespread ipsilateral increase in receptor binding was seen rostrally from the cingulate, olfactory tubercle, and nucleus accumbens, along the lateral hypothalamus and hippocampus, and extending caudally to the substantia nigra and ventral tegmentum. These later effects appear to be related to stimulation-induced changes in blood flow and subsequent ligant presentation increases. Collectively, these data point towards the ability of rewarding brain stimulation to activate discrete neuronal opioid systems contingent upon specific behavioral as well as stimulus conditions.
颅内自我刺激（ICS）被认为可激活参与处理天然强化剂的神经元系统。代谢图谱研究先前已证明，在主动接受刺激与被动接受刺激的动物中，ICS会特异性地激活中枢神经系统（CNS）的一部分结构。由于已知阿片类药物可增强ICS行为及其可能的强化特性，因此本研究探讨了阿片肽作为ICS介导因子的作用问题。对大鼠进行训练，使其按照固定比率（FR）20的时间表对ICS维持的反应进行操作。在反应稳定后，将大鼠分配到主动刺激组或相应的配对刺激组，采用两种强化时间表中的一种（即FR1 - YFR1、FR20 - YFR20或久坐对照组），并通过体内受体占有率推断阿片肽释放情况。放射自显影分析确定了三组结构。在丘脑内侧背核、基底外侧杏仁核、腹侧苍白球、内侧缰核、中缝背核、下丘脑后部、黑质致密部、无颗粒岛叶前皮质和未定带中观察到了治疗引起的占有率变化。根据不同结构，肽释放取决于刺激条件（主动与配对）和/或时间表（FR1与FR20）。在缰核和岛叶前皮质中发现了ICS诱导肽释放受抑制的证据。另外九个结构，均为边缘系统的组成部分或接受其投射，显示出ICS治疗与电极侧之间存在复杂的相互作用。最后，从扣带回、嗅结节和伏隔核开始，沿着下丘脑外侧和海马体，一直到尾侧的黑质和腹侧被盖区，在同侧广泛观察到受体结合增加。这些后期效应似乎与刺激引起的血流变化以及随后配体呈现增加有关。总体而言，这些数据表明，奖励性脑刺激能够根据特定行为和刺激条件激活离散的神经元阿片系统。
