Hatip-Al-khati I, Bölükbasi F, Mishima K, Egashira N, Iwasaki K, Fujiwara M
Department of Pharmacology, Faculty of Medicine, Pamukkale University, Denizli, Turkey.
Jpn J Pharmacol. 2001 Dec;87(4):277-87. doi: 10.1254/jjp.87.277.
We investigated modification of the MK-801 effect on motor activity and extracellular amines concentration by 6-hydroxydopamine (6-OHDA)-induced lesion of core nucleus accumbens (cACC) of rats. In vivo microdialysis-HPLC showed that the concentrations (fmol/microl) of dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and serotonin were 0.738 +/- 0.135, 155.34 +/- 41.01 and 0.334 +/- 0.024, respectively, in the cACC of intact rats. The DOPAC/DA ratio was 264.24 +/- 94.01. Unilateral lesion of the cACC with 6-OHDA (8 microg/microl) substantially reduced DA (-93%) and DOPAC (-97%) in desipramine (30 mg/kg, i.p.)-pretreated rats (6-OHDA+DMI rats) as compared to the 65% reduction rate of both amines in saline-pretreated rats (6-OHDA+saline rats). Moreover, DOPAC was reduced by 72% in 6-OHDA+DMI rats. MK-801 increased DOPAC (426-467%) and DOPAC/DA ratio (180-230%) in intact rats. On the other hand, MK-801 increased DA by 154% and 505% in 6-OHDA+saline and 6-OHDA+DMI rats, respectively. 6-OHDA reduced the effect of MK-801 on DOPAC and DOPAC/DA ratio. In the behavioral studies, MK-801 (0.01-0.3 mg/kg, i.p.) increased locomotor activity and rearing of intact rats. Bilateral 6-OHDA+DMI lesion of the cACC caused greater reduction in the effect of MK-801 (0.1 mg/kg) than that of the shell nucleus accumbens. These results suggest that increased extracellular DOPAC concentration (but not DA) and DOPAC/DA ratio in the cACC plays an important role in MK-801-hyperactivity.
我们研究了6-羟基多巴胺（6-OHDA）诱导大鼠伏隔核核心（cACC）损伤对MK-801运动活性及细胞外胺类浓度的影响。体内微透析-高效液相色谱法显示，完整大鼠cACC中多巴胺（DA）、二羟基苯乙酸（DOPAC）和5-羟色胺的浓度（fmol/μl）分别为0.738±0.135、155.34±41.01和0.334±0.024。DOPAC/DA比值为264.24±94.01。与盐水预处理大鼠（6-OHDA+盐水大鼠）中两种胺类65%的降低率相比，用6-OHDA（8μg/μl）单侧损伤cACC可使去甲丙咪嗪（30mg/kg，腹腔注射）预处理大鼠（6-OHDA+DMI大鼠）的DA（-93%）和DOPAC（-97%）大幅降低。此外，6-OHDA+DMI大鼠的DOPAC降低了72%。MK-801可使完整大鼠的DOPAC（增加426%-467%）和DOPAC/DA比值（增加180%-230%）升高。另一方面，MK-801可使6-OHDA+盐水大鼠和6-OHDA+DMI大鼠的DA分别增加154%和505%。6-OHDA减弱了MK-801对DOPAC和DOPAC/DA比值的影响。在行为学研究中，MK-801（0.01-0.3mg/kg，腹腔注射）可增加完整大鼠的运动活性和竖毛行为。cACC的双侧6-OHDA+DMI损伤比伏隔核壳核损伤对MK-801（0.1mg/kg）作用的减弱程度更大。这些结果表明，cACC中细胞外DOPAC浓度（而非DA）和DOPAC/DA比值的升高在MK-801诱导的多动中起重要作用。
