Lakshmana M K, Rao B S, Dhingra N K, Ravikumar R, Sudha S, Meti B L, Raju T R
Department of Neurophysiology, National Institute of Mental Health and Neurosciences, Bangalore, India.
Neurochem Res. 1998 Aug;23(8):1031-7. doi: 10.1023/a:1020799700885.
The role of monoamine oxidase (MAO) type A and B on the metabolism of dopamine (DA) in discrete regions of the monkey brain was studied. Monkeys were administered (-)-deprenyl (0.25 mg/kg) or clorgyline (1.0 mg/kg) or deprenyl and clorgyline together by intramuscular injections for 8 days. Levels of DA and its metabolites, dihydroxy phenylacetic acid (DOPAC) and homovanillic acid (HVA) were estimated in frontal cortex (FC), motor cortex (MC), occipital cortex (OC), entorhinal cortex (EC), hippocampus (HI), hypothalamus (HY), caudate nucleus (CN), globus pallidus (GP) and substantia nigra (SN). (-)-Deprenyl administration significantly increased DA levels in FC, HY, CN, GP and SN (39-87%). This was accompanied by a reduction in the levels of DOPAC (37-66%) and HVA (27-79%). Clorgyline administration resulted in MAO-A inhibition by more than 87% but failed to increase DA levels in any of the brain regions studied. Combined treatment of (-)-deprenyl and clorgyline inhibited both types of MAO by more than 90% and DA levels were increased (57-245%) in all brain regions studied with a corresponding decrease in the DOPAC (49-83%) and HVA (54-88%) levels. Our results suggest that DA is metabolized preferentially, if not exclusively by MAO-B in some regions of the monkey brain.
研究了单胺氧化酶(MAO)A 型和 B 型对猴脑离散区域中多巴胺(DA)代谢的作用。通过肌肉注射给猴子连续 8 天给予(-)-司来吉兰(0.25mg/kg)或氯吉兰(1.0mg/kg)或两者联合使用。测定额叶皮质(FC)、运动皮质(MC)、枕叶皮质(OC)、内嗅皮质(EC)、海马(HI)、下丘脑(HY)、尾状核(CN)、苍白球(GP)和黑质(SN)中 DA 及其代谢产物二羟基苯乙酸(DOPAC)和高香草酸(HVA)的水平。给予(-)-司来吉兰显著增加了 FC、HY、CN、GP 和 SN 中的 DA 水平(39%-87%)。这伴随着 DOPAC 水平(37%-66%)和 HVA 水平(27%-79%)的降低。给予氯吉兰导致 MAO-A 抑制超过 87%,但在所研究的任何脑区均未增加 DA 水平。(-)-司来吉兰和氯吉兰联合治疗抑制了两种类型的 MAO 超过 90%,并且在所研究的所有脑区 DA 水平均升高(57%-245%),同时 DOPAC(49%-83%)和 HVA(54%-88%)水平相应降低。我们的结果表明,在猴脑的某些区域,DA 优先(如果不是唯一地)由 MAO-B 代谢。