Fibiger H C, LePiane F G, Jakubovic A, Phillips A G
Department of Psychiatry, University of British Columbia, Vancouver, Canada.
J Neurosci. 1987 Dec;7(12):3888-96. doi: 10.1523/JNEUROSCI.07-12-03888.1987.
The role of dopaminergic (DA) neurons in brain stimulation reward produced by electrical stimulation of the ventral tegmental area (VTA) was investigated in the rat. In the first experiment, extensive 6-hydroxydopamine lesions of the ascending fibers of the mesotelencephalic DA projections resulted in significant changes in intracranial self-stimulation (ICS) rate-current intensity functions when the lesion was ipsilateral to the stimulating electrode. Similar contralateral lesions had no effect on these functions, thus ruling out lesion-induced performance deficits as being responsible for the decreases in ICS rates across the wide range of current intensities that occurred after the ipsilateral lesions. In the second experiment, ICS obtained from electrodes in the VTA resulted in significant increases in the DA metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum, nucleus accumbens, and olfactory tubercle ipsilateral to the stimulating electrode. The ratios of DOPAC and HVA to DA, considered to be indices of DA utilization, were also increased in these brain regions ipsilateral to the electrode. No changes were observed in the contralateral striatum, nucleus accumbens, and olfactory tubercle. Similar increases were observed in stimulated "yoked" animals that received brain stimulation at identical rates and currents but did not lever-press for this stimulation. The third experiment examined the effects of lever-pressing for food on an FR8 schedule of reinforcement on DA utilization in the striatum, nucleus accumbens, and olfactory tubercle. Despite high rates of responding, no effects were observed on DOPAC:DA or HVA:DA ratios in these brain regions.(ABSTRACT TRUNCATED AT 250 WORDS)
在大鼠中研究了多巴胺能（DA）神经元在腹侧被盖区（VTA）电刺激所产生的脑刺激奖赏中的作用。在第一个实验中，当损伤位于刺激电极同侧时，中脑边缘DA投射的升支受到广泛的6-羟基多巴胺损伤，导致颅内自我刺激（ICS）频率-电流强度函数发生显著变化。类似的对侧损伤对这些函数没有影响，从而排除了损伤引起的行为缺陷是导致同侧损伤后在广泛电流强度范围内ICS频率降低的原因。在第二个实验中，从VTA中的电极获得的ICS导致刺激电极同侧的纹状体、伏隔核和嗅结节中DA代谢产物3,4-二羟基苯乙酸（DOPAC）和高香草酸（HVA）显著增加。DOPAC和HVA与DA的比率被认为是DA利用的指标，在电极同侧的这些脑区中也增加了。在对侧纹状体、伏隔核和嗅结节中未观察到变化。在以相同频率和电流接受脑刺激但不为此刺激进行杠杆按压的受刺激“配对”动物中也观察到了类似的增加。第三个实验研究了在固定比率为8的强化程序下按压杠杆获取食物对纹状体、伏隔核和嗅结节中DA利用的影响。尽管反应率很高，但在这些脑区中未观察到对DOPAC:DA或HVA:DA比率的影响。（摘要截短于250字）
