Department of Psychology, Kenyon College, Gambier, OH 43022, USA.
Brain Res. 2011 Oct 28;1420:29-36. doi: 10.1016/j.brainres.2011.08.054. Epub 2011 Aug 27.
Lithium exerts anti-dopaminergic behavioral effects. We examined whether some of these might be mediated by changes in brain levels of tyrosine (TYR), the precursor to dopamine. Lithium chloride (LiCl(2)) 3.0mEq/kg IP acutely lowered serum TYR and the ratio of serum TYR to other large neutral amino acids (LNAAs); it also selectively lowered striatum TYR levels as measured in tissue or in vivo. While LiCl(2) 3.0mEq/kg IP also augmented haloperidol (0.19mg/kg SC)-induced catalepsy, this lithium effect was not attenuated by administration of TYR 100mg/kg IP. We conclude that lithium acutely and selectively lowers brain TYR by lowering serum levels of tyrosine relative to the LNAAs that compete with it for transport across the blood-brain barrier. However, the lowering of TYR does not appear to significantly contribute to the ability of lithium to potentiate haloperidol-mediated catalepsy.
锂具有抗多巴胺能行为效应。我们研究了这些效应中的某些效应是否可能是通过改变脑中酪氨酸(TYR)的水平(多巴胺的前体)而介导的。氯化锂(LiCl(2))3.0mEq/kg 腹腔内给药可急性降低血清 TYR 和血清 TYR 与其他大中性氨基酸(LNAAs)的比值;它还选择性地降低纹状体 TYR 水平,无论是在组织中还是在体内测量。虽然 LiCl(2)3.0mEq/kg 腹腔内给药也增强了氟哌啶醇(0.19mg/kg 皮下注射)诱导的僵住,但这种锂的作用不会被 TYR 100mg/kg 腹腔内给药所减弱。我们的结论是,锂通过降低相对于与它竞争穿过血脑屏障的 LNAAs 的血清 TYR 水平而急性和选择性地降低脑 TYR。然而,TYR 的降低似乎并没有显著增强锂增强氟哌啶醇介导的僵住的能力。