γ-丁内酯和巴氯芬对多巴胺合成的延迟抑制作用：多巴胺自身受体超敏反应？

Delayed inhibition of dopamine synthesis by gamma-butyrolactone and baclofen: dopamine autoreceptor supersensitivity?

作者信息

Argiolas A, Fadda F, Melis M R, Marcou M, Porceddu M L, Gessa G L

出版信息

Eur J Pharmacol. 1982 Nov 5;85(1):23-7. doi: 10.1016/0014-2999(82)90420-4.

Abstract

The administration of gamma-butyrolactone (GBL) (750 mg . kg-1 i.p.) and baclofen (20 mg . kg-1 i.p.) to rats caused a transient increase followed by a long-lasting decrease in striatal dopamine (DA) synthesis, as measured by DOPA accumulation after decarboxylase inhibition. DA synthesis was reduced to 40-50% of the control value for 2-12 h following either treatment. The GBL- and baclofen-induced inhibition of DN synthesis was reversed by haloperidol (2-5 mg . kg-1 i.p.) and by a second dose of baclofen or GBL. The subcutaneous dose of 15 mg . kg-1 of apomorphine, insufficient to decrease DA synthesis in control rats, produced a further decrease in DA synthesis in animals pretreated with baclofen. These results suggest that the delayed DA synthesis inhibition following GBL or baclofen treatment was due to stimulation of supersensitive DA autoreceptors.

摘要

给大鼠腹腔注射γ-丁内酯（GBL）（750毫克·千克-1）和巴氯芬（20毫克·千克-1）后，通过抑制脱羧酶后多巴（DOPA）积累来测量，纹状体多巴胺（DA）合成先出现短暂增加，随后出现长期下降。两种处理后，DA合成在2至12小时内降至对照值的40 - 50%。氟哌啶醇（2 - 5毫克·千克-1腹腔注射）以及第二剂巴氯芬或GBL可逆转GBL和巴氯芬诱导的DA合成抑制。皮下注射15毫克·千克-1的阿扑吗啡，剂量不足以降低对照大鼠的DA合成，但在用巴氯芬预处理的动物中，可使DA合成进一步降低。这些结果表明，GBL或巴氯芬处理后DA合成的延迟抑制是由于超敏DA自身受体的刺激。