Gunne L M, Häggström J E, Johansson P, Levin E D, Terenius L
Psychiatric Research Center, Ulleråker Hospital, Uppsala, Sweden.
Encephale. 1988 Sep;14 Spec No:167-73.
There is evidence for the view that both up- and downregulation of nigral GABA may give rise to dyskinetic movements. Intranigral infusion of GABA agonists causes stereotyped licking and gnawing in rats, while intranigral GABA antagonists produce vacuous chewing movements. It is hypothesized that during long-term neuroleptic treatment there may be a succession of changes within striatonigral GABA neurons: down-regulation caused by neuroleptic drugs may increase receptor sensitivity, and this may lead to overcompensation and withdrawal dyskinesia during periods of cessation of drug treatment. Reduced nigral GAD activity may be a marker of irreversible brain damage and has not been observed in all chronic experiments, but only in individuals with long-standing or irreversible dyskinesia. Changes within the GABA system seem to be accompanied by changes in the striatal and nigral levels of substance P.
有证据支持这样一种观点，即黑质γ-氨基丁酸（GABA）的上调和下调都可能导致运动障碍。向黑质内注射GABA激动剂会使大鼠出现刻板的舔舐和啃咬动作，而向黑质内注射GABA拮抗剂则会产生空嚼运动。据推测，在长期使用抗精神病药物治疗期间，纹状体黑质GABA能神经元可能会发生一系列变化：抗精神病药物引起的下调可能会增加受体敏感性，这可能会导致在药物治疗停止期间出现过度补偿和撤药运动障碍。黑质谷氨酸脱羧酶（GAD）活性降低可能是不可逆脑损伤的一个标志，并非在所有慢性实验中都能观察到，而仅在患有长期或不可逆运动障碍的个体中出现。GABA系统内的变化似乎伴随着P物质在纹状体和黑质水平的变化。
