Zito K A, Vickers G, Roberts D C
Pharmacol Biochem Behav. 1985 Dec;23(6):1029-36. doi: 10.1016/0091-3057(85)90110-8.
In previous experiments we have demonstrated that bilateral infusions of 6-hydroxydopamine (6-OHDA) into the nucleus accumbens result in a drastic reduction in the rate of cocaine self-administration. If this effect is due to the destruction of a presynaptic dopaminergic element in this nucleus, then selective removal of the postsynaptic neuron should also disrupt cocaine self-administration. This hypothesis was tested using the neurotoxin kainic acid. Bilateral kainic acid infusions into the nucleus accumbens resulted in a drastic destruction of cell bodies yet did not damage catecholamine innervation in areas anterior to the accumbens. The effects of these kainic acid infusions were evaluated in rats that had previously acquired cocaine self-administration behavior. These lesions were found to severely disrupt cocaine intake and the degree of damage produced in the accumbens was found to correlate (r = 0.88) with postlesion cocaine intake. These lesions were additionally found to disrupt apomorphine and heroin self-administration. The possibility that these results are due to destruction of systems necessary for stimulant and opiate reward is discussed.
在先前的实验中,我们已经证明,向伏隔核双侧注射6-羟基多巴胺(6-OHDA)会导致可卡因自我给药率大幅降低。如果这种效应是由于该核中突触前多巴胺能元件的破坏,那么选择性去除突触后神经元也应该会扰乱可卡因自我给药。使用神经毒素 kainic 酸对这一假设进行了测试。向伏隔核双侧注射 kainic 酸导致细胞体严重受损,但并未损害伏隔核前方区域的儿茶酚胺神经支配。在先前已经习得可卡因自我给药行为的大鼠中评估了这些 kainic 酸注射的效果。发现这些损伤严重扰乱了可卡因摄入,并且发现伏隔核中产生的损伤程度与损伤后可卡因摄入量相关(r = 0.88)。还发现这些损伤扰乱了阿扑吗啡和海洛因自我给药。讨论了这些结果是否由于破坏了兴奋剂和阿片类药物奖赏所必需的系统。