Callahan P M, De La Garza R, Cunningham K A
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77555-1031, USA.
Pharmacol Biochem Behav. 1997 Jul;57(3):601-7. doi: 10.1016/s0091-3057(96)00434-0.
This paper provides a brief review of the scientific evidence implicating the mesocorticolimbic dopamine (DA) system in modulating the discriminative stimulus properties of cocaine in rats. Briefly, systemic administration of DA releasers, reuptake inhibitors, and DA D1, D2, and putative D3 receptor agonists engendered partial to full substitution for the discriminative stimulus effects of cocaine. Dopamine D1 and D2 receptor antagonists attenuate this behavioral property of cocaine. Intracranial microinjection studies have indicated certain key limbic nuclei us loci of action for DA in mediating the discriminative stimulus effects of cocaine. Microinjections of cocaine into either DA cell body (i.e., ventral tegmental area, substantia nigra) or DA terminal regions (i.e., prefrontal cortex, central amygdala, caudate putamen) have failed to reproduce the systemic cocaine discriminative stimulus. Only infusion of cocaine into the nucleus accumbens has been demonstrated to substitute fully for the systemic effects of this psychostimulant. Interestingly, microinjections of the DA D1 receptor antagonist SCH 23390 into either the prefrontal cortex, nucleus accumbens, or central or basolateral amygdala have been demonstrated to block the discriminative stimulus properties of cocaine. Although a determination of the antagonism of the cocaine discriminative stimulus following intra-accumbens microinjection of DA D2 receptor antagonists has not been made, intra-accumbens administration of the DA D2 receptor antagonist sulpiride blocked the discriminative stimulus effects of another psychostimulant, amphetamine. 6-Hydroxydopamine lesions of DA terminals in the nucleus accumbens also attenuated the dose-effect curve for systemic administration of cocaine. Taken together, this intracranial evidence suggests that DA D1 and D2 receptors in the mesocorticolimbic system are involved in modulating the discriminative stimulus properties of psychostimulants and that the nigrostriatal DA system is not primarily involved.
本文简要综述了有关中脑边缘多巴胺（DA）系统在调节大鼠可卡因辨别性刺激特性方面的科学证据。简而言之，全身给予DA释放剂、再摄取抑制剂以及DA D1、D2和假定的D3受体激动剂会产生部分至完全替代可卡因辨别性刺激效应的情况。多巴胺D1和D2受体拮抗剂会减弱可卡因的这种行为特性。颅内微量注射研究表明，某些关键的边缘核是DA介导可卡因辨别性刺激效应的作用位点。向DA细胞体（即腹侧被盖区、黑质）或DA终末区域（即前额叶皮质、中央杏仁核、尾状壳核）微量注射可卡因未能重现全身可卡因的辨别性刺激。仅向伏隔核输注可卡因已被证明可完全替代这种精神兴奋剂的全身效应。有趣的是，已证明向前额叶皮质、伏隔核或中央或基底外侧杏仁核微量注射DA D1受体拮抗剂SCH 23390可阻断可卡因的辨别性刺激特性。尽管尚未确定伏隔核内微量注射DA D2受体拮抗剂后对可卡因辨别性刺激的拮抗作用，但伏隔核内给予DA D2受体拮抗剂舒必利可阻断另一种精神兴奋剂苯丙胺的辨别性刺激效应。伏隔核中DA终末的6-羟基多巴胺损伤也减弱了全身给予可卡因的剂量-效应曲线。综上所述，这些颅内证据表明，中脑边缘系统中的DA D1和D2受体参与调节精神兴奋剂的辨别性刺激特性，而黑质纹状体DA系统并非主要参与其中。
