Campochiaro P, Schwarcz R, Coyle J T
Brain Res. 1977 Nov 18;136(3):501-11. doi: 10.1016/0006-8993(77)90074-9.
Intrastriatal injection of 2 microgram of kainic acid, a conformationally restricted analogue of glutamate, causes degeneration of GABAergic neurons intrinsic to the striatum while sparing axons of extrinsic neurons terminating in or passing through the region. From 2 to 15 days after striatal lesion with kainate, the sodium-independent binding of [3H]-psi-aminobutyric acid (GABA) to striatal membranes is increased 200% above that of control. Differences in the amount of endogenous GABA contaminating the membrane preparations do not account for the increased receptor binding. Scatchard analysis reveals an increased affinity of the GABA receptor in the kainate-lesioned striatum with no change in the number of binding sites. The subcellular distribution of the receptor as well as the sensitivity of the receptor to several agonists and antagonists is unchanged by the kainate lesion. Ablation of the nigrostriatal dopaminergic pathway by nigral injection of 8 microgram of 6-hydroxydopamine reduces by 22% the specific binding of [3H]GABA in the ipsilateral striatum and attenuates by 33% the increase in GABA receptor binding produced by the striatal kainate lesion. These studies demonstrate that (1) the sodium independent binding sites for GABA in striatum are localized on axons of extrinsic neurons, and (2) the affinity of these receptors for GABA increases in response to GABAergic denervation.
向纹状体内注射2微克红藻氨酸（一种结构受限的谷氨酸类似物）会导致纹状体内固有的γ-氨基丁酸（GABA）能神经元变性，同时使终止于该区域或穿过该区域的外在神经元的轴突不受影响。在用红藻氨酸造成纹状体损伤后的2至15天内，[3H]-ψ-氨基丁酸（GABA）与纹状体膜的非钠依赖性结合比对照组增加了200%。膜制剂中内源性GABA污染量的差异并不能解释受体结合的增加。Scatchard分析显示，红藻氨酸损伤的纹状体中GABA受体的亲和力增加，而结合位点的数量没有变化。红藻氨酸损伤对受体的亚细胞分布以及受体对几种激动剂和拮抗剂的敏感性没有影响。通过向黑质注射8微克6-羟基多巴胺来损毁黑质纹状体多巴胺能通路，可使同侧纹状体中[3H]GABA的特异性结合减少22%，并使纹状体红藻氨酸损伤所产生的GABA受体结合增加减弱33%。这些研究表明：（1）纹状体中GABA的非钠依赖性结合位点位于外在神经元的轴突上；（2）这些受体对GABA的亲和力会因GABA能去神经支配而增加。
