Kleven M S, Perry B D, Woolverton W L, Seiden L S
Department of Pharmacological and Physiological Sciences, University of Chicago, IL 60637.
Brain Res. 1990 Nov 5;532(1-2):265-70. doi: 10.1016/0006-8993(90)91768-c.
In order to determine if chronic administration of cocaine produced long-lasting alterations in dopamine receptor binding, rats were treated with single daily injections of cocaine (0, 10, or 20 mg/kg) for 15 consecutive days and killed either 20 min or 2 weeks after the last injection. The density of D1 binding sites in frontal cortex was either unchanged (10 mg/kg) or slightly increased (20 mg/kg) 20 min after the last daily injection, but was decreased 2 weeks later. D1 sites in striatum were decreased both immediately and 2 weeks after the injection regimen. Decreases in D1 binding site density in nucleus accumbens were observed only immediately after the last injection. In contrast to these effects on D1 binding sites, D2 binding sites were decreased in striatum and frontal cortex and increased in the nucleus accumbens 20 min after repeated cocaine, but were unaffected 2 weeks after repeated cocaine. Computer-assisted analysis of the saturation isotherms revealed that chronic administration of cocaine did not affect the affinity (Kd) of the radioligands used to label D1 or D2 sites. These findings suggest that repeated administration of cocaine results in long-term decreases in D1 binding sites in striatum and frontal cortex and transient decreases in D2 binding sites. Furthermore, cocaine caused opposite, transient effects on D1 and D2 site density in nucleus accumbens.
为了确定长期给予可卡因是否会对多巴胺受体结合产生持久改变，将大鼠连续15天每日单次注射可卡因（0、10或20毫克/千克），并在最后一次注射后20分钟或2周处死。末次每日注射后20分钟，额叶皮质中D1结合位点的密度要么未改变（10毫克/千克），要么略有增加（20毫克/千克），但在2周后降低。纹状体中的D1位点在注射方案后立即和2周后均降低。伏隔核中D1结合位点密度的降低仅在最后一次注射后立即观察到。与对D1结合位点的这些影响相反，重复给予可卡因后20分钟，纹状体和额叶皮质中的D2结合位点减少，伏隔核中的D2结合位点增加，但重复给予可卡因2周后未受影响。对饱和等温线的计算机辅助分析表明，长期给予可卡因不会影响用于标记D1或D2位点的放射性配体的亲和力（Kd）。这些发现表明，重复给予可卡因会导致纹状体和额叶皮质中D1结合位点的长期减少以及D2结合位点的短暂减少。此外，可卡因对伏隔核中D1和D2位点密度产生相反的短暂影响。
