Farfel G M, Kleven M S, Woolverton W L, Seiden L S, Perry B D
Department of Pharmacological and Physiological Sciences, University of Chicago, IL 60637.
Brain Res. 1992 Apr 24;578(1-2):235-43. doi: 10.1016/0006-8993(92)90252-5.
In order to determine if repeated injections of cocaine produced long-lasting alterations in catecholaminergic binding sites, rhesus monkeys were treated with saline (1.0 ml/15 kg) or cocaine (3.0-4.0 mg/kg) four times daily for 14 consecutive days and sacrificed two weeks after the last injection. The densities of dopamine D1 receptor binding sites, dopamine transporter binding sites and beta adrenergic receptor binding sites were significantly decreased in caudate nucleus to 51%, 17% and 61% of control, respectively, two weeks after repeated cocaine injections. There were no differences in D2 receptor binding site densities in the caudate, nor were there differences in binding sites between groups in the other brain regions examined: prefrontal cortex (D1, D2, dopamine transporter, beta), nucleus accumbens (D1, D2, dopamine transporter) and substantia nigra (D2). Behavioral observation showed that the cocaine-treated monkeys became sensitized to the repeated injections. Early in the regimen, these animals displayed stereotypic grooming, buccal movements and visual checking after each injection that differed significantly from the saline-treated animals. As the regimen progressed, the frequency of grooming decreased while the frequencies of visual tracking and splayed legs increased in a manner consistent with the development of behavioral sensitization. Together, these findings suggest that the caudate nucleus may be more sensitive than other dopamine-containing brain regions to long-lasting pre- and post-synaptic effects of repeated cocaine administration, and that the changes seen in dopaminergic neurons may be related to behavioral sensitization.
为了确定反复注射可卡因是否会对儿茶酚胺能结合位点产生持久改变，对恒河猴每日4次给予生理盐水（1.0毫升/15千克）或可卡因（3.0 - 4.0毫克/千克），连续14天，并在最后一次注射后两周处死。反复注射可卡因两周后，尾状核中多巴胺D1受体结合位点、多巴胺转运体结合位点和β肾上腺素能受体结合位点的密度分别显著降低至对照的51%、17%和61%。尾状核中D2受体结合位点密度在各组间无差异，在其他检查的脑区（前额叶皮质（D1、D2、多巴胺转运体、β）、伏隔核（D1、D2、多巴胺转运体）和黑质（D2））的结合位点在各组间也无差异。行为观察表明，经可卡因处理的猴子对反复注射产生了敏感化。在给药初期，这些动物每次注射后都会出现刻板的梳理毛发、颊部运动和视觉检查，这与经生理盐水处理的动物有显著差异。随着给药过程的推进，梳理毛发的频率降低，而视觉追踪和叉开腿的频率增加，这与行为敏感化的发展一致。这些发现共同表明，尾状核可能比其他含多巴胺的脑区对反复给予可卡因的持久突触前和突触后效应更敏感，并且在多巴胺能神经元中观察到的变化可能与行为敏感化有关。
