Masserano J M, Venable D, Wyatt R J
Neuropsychiatry Branch, National Institute of Mental Health Neurosciences Center at St. Elizabeths, Washington, District of Columbia.
J Pharmacol Exp Ther. 1994 Jul;270(1):133-41.
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.
在用可卡因进行慢性治疗后，评估了从伏隔核、纹状体和额叶皮质获得的突触体对[3H]多巴胺的摄取情况。可卡因以10毫克/千克的浓度给药，每天两次，持续7天。最后一次注射后14天，评估运动活性和[3H]多巴胺摄取情况。与用生理盐水处理的大鼠相比，长期用可卡因处理的大鼠的基线运动活性显著降低（29%）。可卡因（2.5毫克/千克或5.0毫克/千克）或右旋苯丙胺（1毫克/千克）的激发剂量在生理盐水处理和可卡因处理的大鼠中均使运动活性比相应的基线值有类似程度的增加，表明未发生行为敏化。长期给予可卡因使额叶皮质中[3H]多巴胺的摄取显著减少（49%），而伏隔核或纹状体中无显著差异。额叶皮质中[3H]多巴胺摄取的减少是由于Vmax降低，而[3H]多巴胺对多巴胺转运体的亲和力没有变化。长期给予可卡因后，GBR 12909或可卡因对[3H]多巴胺摄取的IC50值没有差异。然而，在所有三个脑区中，可卡因的IC50值均显著高于GBR 12909的值。此外，额叶皮质中GBR 12909和可卡因的IC50值显著高于伏隔核或纹状体中任何一种化合物的值。采用类似的给药方案给予甲基苯丙胺，在三个脑区中的任何一个脑区[3H]多巴胺摄取均未发生变化。这些数据表明重复给予可卡因对大鼠额叶皮质中[3H]多巴胺摄取有抑制作用。
