De Leonibus E, Mele A, Oliverio A, Pert A
Dipartimento di Genetica e Biologia Molecolare, Università di Roma "La Sapienza", Ple. Aldo Moro 5, I-00185, Rome, Italy.
Neuroscience. 2001;104(1):105-16. doi: 10.1016/s0306-4522(01)00047-1.
We have recently shown that focal administration of dizocilpine hydrogen maleate (MK-801, a non-competitive N-methyl-D-aspartate antagonist) within the nucleus accumbens increases locomotor activity in a dopamine-independent manner. The purpose of this study was to investigate the neural network underlying locomotor stimulation induced by N-methyl-D-aspartate receptor blockade in the accumbens. In the first experiment, we examined the effect of different doses (1, 5 and 25 nmol) of the active and inactive enantiomers of the N-methyl-D-aspartate antagonist, (+)- and (-)-MK-801, respectively, focally administered in the nucleus accumbens. Only the active enantiomer induced a significant increase in locomotor activity; furthermore, the effect induced by the two highest doses of (+)-MK-801 was significantly different from that induced by (-)-MK-801. In the second part of the study, we performed ibotenic acid lesions to the major output nuclei of the accumbens, the ventral pallidum, mediodorsal thalamus, ventrolateral/ventromedial thalamus and pedunculopontine tegmental nucleus, to observe their effect on locomotor activity induced by focal (+)-MK-801 (25 nmol) administration into the accumbens. None of the lesions had any effect on spontaneous locomotor activity. Hyperactivity induced by accumbens MK-801 administrations was unaffected by ibotenic acid lesions of the pedunculopontine tegmental nucleus, while lesions of the mediodorsal thalamus induced only a partial inhibition. In contrast, ibotenic acid lesions of the ventral pallidum and ventrolateral/ventromedial thalamus completely blocked the motor response induced by accumbens MK-801. These data indicate that the intact mediodorsal thalamus, which has been proposed as a part of the loop that relays accumbens information to the prefrontal cortex, does not seem to be a structure of primary importance in MK-801 locomotor activity. On the contrary, the motor nuclei of the thalamus appear to play a more relevant role, suggesting that different neural substrates may mediate dopamine and glutamate functional output from the nucleus accumbens.
我们最近发现，在伏隔核局部注射马来酸氢二氮卓（MK-801，一种非竞争性N-甲基-D-天冬氨酸拮抗剂）能以不依赖多巴胺的方式增加运动活性。本研究的目的是探究伏隔核中N-甲基-D-天冬氨酸受体阻断诱导运动刺激的神经网络。在第一个实验中，我们分别检测了将不同剂量（1、5和25纳摩尔）的N-甲基-D-天冬氨酸拮抗剂的活性和非活性对映体，即（+）-和（-）-MK-801，局部注射到伏隔核中的效果。只有活性对映体能显著增加运动活性；此外，两种最高剂量的（+）-MK-801所诱导的效果与（-）-MK-801所诱导的效果显著不同。在研究的第二部分，我们对伏隔核的主要输出核团，即腹侧苍白球、背内侧丘脑、腹外侧/腹内侧丘脑和脚桥被盖核进行鹅膏蕈氨酸损伤，以观察它们对向伏隔核局部注射（+）-MK-801（25纳摩尔）所诱导的运动活性的影响。这些损伤对自发运动活性均无任何影响。伏隔核注射MK-801所诱导的多动不受脚桥被盖核鹅膏蕈氨酸损伤的影响，而背内侧丘脑损伤仅诱导部分抑制。相反，腹侧苍白球和腹外侧/腹内侧丘脑的鹅膏蕈氨酸损伤完全阻断了伏隔核MK-801诱导的运动反应。这些数据表明，完整的背内侧丘脑，虽被认为是将伏隔核信息传递到前额叶皮质的环路的一部分，但似乎并非MK-801运动活性中至关重要的结构。相反，丘脑的运动核团似乎发挥着更相关的作用，这表明不同的神经基质可能介导伏隔核的多巴胺和谷氨酸功能输出。
