Kogan F J, Nichols W K, Gibb J W
Eur J Pharmacol. 1976 Apr;36(2):363-71. doi: 10.1016/0014-2999(76)90090-x.
In previous reports, methamphetamine was shown to depress tyrosine hydroxylase (TH) activity in the rat corpus striatum. To evaluate further the mechanism of this decrease in TH activity, enzyme activity was measured in the rat corpus striatum and substantia nigra after repetitive and single-dose methamphetamine administration. Following repeated doses of methamphetamine, nigral TH activity decreased and reached 45% of controls at 12 hr and returned to normal at 60 hr. Striatal TH activity decreased to 40% of control at 36 hr and returned toward normal at 60 hr. When methamphetamine was administered every 6 hr for 30 hr and then discontinued, nigral TH activity returned toward control levels 4 days prior to recovery of striatal TH activity. Methamphetamine initially increased striatal dopamine levels at 6 hr (170% of control). Dopamine levels then decreased in parallel with striatal TH activity but failed to increase as the enzyme recovered. Concurrent administration of chlorpromazine with methamphetamine prevented the methamphetamine-induced decrease in nigral and striatal TH activity and striatal dopamine levels. The results indicate that the methamphetamine-induced depression of striatal and nigral TH activity may be related to increased stimulation of dopamine receptors in the striatum.
在先前的报告中，已表明甲基苯丙胺可抑制大鼠纹状体中的酪氨酸羟化酶（TH）活性。为了进一步评估TH活性降低的机制，在重复给药和单剂量给予甲基苯丙胺后，测定了大鼠纹状体和黑质中的酶活性。重复给予甲基苯丙胺后，黑质TH活性降低，在12小时时降至对照组的45%，并在60小时时恢复正常。纹状体TH活性在36小时时降至对照组的40%，并在60小时时恢复至接近正常水平。当每6小时给予甲基苯丙胺30小时然后停药时，黑质TH活性在纹状体TH活性恢复前4天恢复至接近对照水平。甲基苯丙胺最初在6小时时使纹状体多巴胺水平升高（为对照组的170%）。然后多巴胺水平与纹状体TH活性平行下降，但在酶活性恢复时未能升高。氯丙嗪与甲基苯丙胺同时给药可防止甲基苯丙胺引起的黑质和纹状体TH活性以及纹状体多巴胺水平的降低。结果表明，甲基苯丙胺引起的纹状体和黑质TH活性降低可能与纹状体中多巴胺受体的刺激增加有关。
