Frey J M, Ticku M K, Huffman R D
Department of Pharmacology, University of Texas Health Science Center at San Antonio, TX 78284-7764.
Brain Res. 1987 Nov 3;425(1):73-84. doi: 10.1016/0006-8993(87)90485-9.
These studies were performed to evaluate the effects of chronic haloperidol administration on the responsiveness of the pars reticulata neurons of the substantia nigra (SNR) to microiontophoretically applied gamma-aminobutyric acid (GABA) and glycine. Rats were administered haloperidol in their feed (CHAL treatment) for 30 days in increasing concentrations. All experiments were conducted two days after termination of the CHAL treatment. GABA receptor binding and neuronal responsiveness to GABA were significantly increased within the SNR following CHAL treatment. The mean EC50 value for GABA was significantly decreased for SNR neurons in CHAL-treated rats, but there was no change in the EC50 for glycine. Specific [3H]GABA binding (4 nM) was elevated by more than 50% within the SNR. Scatchard analysis of [3H]muscimol binding data revealed that the binding capacities (Bmax) of both high and low affinity GABA binding sites within the SNR were significantly increased without a change in the apparent dissociation constants (Kd) of either site. Although no regional difference in responsiveness to GABA was detected within the SNR of CHAL-treated rats, the spontaneous activity of neurons located within the rostral two-thirds of the nucleus was reduced; however, there was no change in spontaneous activity of neurons located within the caudal one-third. These data provide direct physiological evidence to support the conclusion that the increase in GABA binding within the SNR following CHAL treatment reflects a neuronal supersensitivity to GABA.
进行这些研究是为了评估长期给予氟哌啶醇对黑质网状部（SNR）神经元对微量离子导入的γ-氨基丁酸（GABA）和甘氨酸反应性的影响。给大鼠在饲料中添加氟哌啶醇（CHAL处理），浓度逐渐增加，持续30天。所有实验均在CHAL处理结束两天后进行。CHAL处理后，SNR内的GABA受体结合和神经元对GABA的反应性显著增加。CHAL处理的大鼠中，SNR神经元对GABA的平均半数有效浓度（EC50）值显著降低，但甘氨酸的EC50没有变化。SNR内特异性[3H]GABA结合（4 nM）升高超过50%。对[3H]蝇蕈醇结合数据进行Scatchard分析表明，SNR内高亲和力和低亲和力GABA结合位点的结合容量（Bmax）均显著增加，而两个位点的表观解离常数（Kd）均无变化。虽然在CHAL处理的大鼠SNR内未检测到对GABA反应性的区域差异，但位于核前三分之二的神经元的自发活动降低；然而，位于尾三分之一的神经元的自发活动没有变化。这些数据提供了直接的生理学证据，支持CHAL处理后SNR内GABA结合增加反映神经元对GABA超敏反应这一结论。
