Effects of chronic cocaine administration on [3H]dopamine uptake in the nucleus accumbens, striatum and frontal cortex of rats.
Effects of chronic cocaine administration on [3H]dopamine uptake in the nucleus accumbens, striatum and frontal cortex of rats.
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长期服用可卡因对大鼠伏隔核、纹状体和额叶皮层[3H]多巴胺摄取的影响。
DOI：
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发表时间：
1994
影响因子：
3.5
通讯作者：
R. Wyatt
中科院分区：
文献类型：
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作者：
J. Masserano;D. Venable;R. Wyatt
用可卡因慢性处理后，观察伏隔核、纹状体和额叶皮质突触小体对[~3H]多巴胺的摄取。可卡因浓度为10 mg/kg，每日两次，连续7天。最后一次注射后14天，测定大鼠的运动能力和[~3H]多巴胺摄取。与生理盐水处理的大鼠相比，长期使用可卡因的大鼠的基线运动活动显著降低(29%)。攻击剂量的可卡因(2.5 mg/kg或5.0 mg/kg)或d-苯丙胺(1 mg/kg)在生理盐水和可卡因处理的大鼠中都能产生高于相应基线的类似的运动活动增加，表明行为敏化没有发生。长期服用可卡因可使额叶皮质对[~3H]多巴胺的摄取显著减少(49%)，而伏隔核和纹状体的摄取无明显差异。额叶皮质对[~3H]多巴胺摄取的减少是由于Vmax的降低，而[~3H]多巴胺与多巴胺转运体的亲和力没有改变。慢性可卡因处理后，GBR 12909和可卡因对[3 H]多巴胺摄取的IC_(50)值无差异。然而，在所有三个大脑区域，可卡因的IC50值都显著高于12909英镑的值。此外，GBR 12909和可卡因在额叶皮质的IC50值明显大于伏隔核或纹状体中任何一种化合物的IC50值。服用甲基苯丙胺，使用类似的治疗程序，在三个大脑区域中的任何一个区域没有产生[~3H]多巴胺摄取的变化。这些数据表明，反复给予可卡因对大鼠额叶皮质的[~3H]多巴胺摄取有抑制作用。
The uptake of [3H]dopamine into synaptosomes obtained from the nucleus accumbens, striatum and frontal cortex was evaluated after chronic treatment with cocaine. Cocaine was administered in a concentration of 10 mg/kg, twice a day for 7 days. Fourteen days after the last injection, locomotor activity and [3H] dopamine uptake were evaluated. Base-line locomotor activity was significantly lower (29%) in rats treated chronically with cocaine compared with saline-treated rats. A challenge dose of cocaine (2.5 mg/kg or 5.0 mg/kg) or d-amphetamine (1 mg/kg) produced similar increases in locomotor activity above the corresponding base-line values in both saline- and cocaine-treated rats, indicating that behavioral sensitization had not occurred. Chronic cocaine administration produced a significant decrease in the uptake of [3H]dopamine into the frontal cortex (49%) with no significant differences in the nucleus accumbens or striatum. The decrease in [3H]dopamine uptake in the frontal cortex was due to a decrease in the Vmax with no change in the affinity of [3H]dopamine for the dopamine transporter. No differences were produced in the IC50 values of GBR 12909 or cocaine for [3H] dopamine uptake after chronic cocaine treatment. However, in all three brain regions, the IC50 values for cocaine were significantly greater than the values for GBR 12909. In addition, the IC50 values for GBR 12909 and cocaine in the frontal cortex were significantly greater than values for either compound in the nucleus accumbens or striatum. The administration of methamphetamine, using a similar treatment schedule, produced no changes in [3H]dopamine uptake in any of the three brain areas. These data indicate an inhibition effect of repeated cocaine administration on [3H]dopamine uptake in the frontal cortex of rats.