Achat-Mendes Cindy, Platt Donna M, Newman Amy H, Spealman Roger D
Division of Neuroscience, New England Primate Research Center, Harvard Medical School, One Pine Hill Dr., P.O. Box 9102, Southborough, MA 01772, USA.
Psychopharmacology (Berl). 2009 Sep;206(1):73-84. doi: 10.1007/s00213-009-1581-9. Epub 2009 Jun 10.
Dopamine D3 receptor mechanisms have been implicated in the abuse-related behavioral effects of cocaine.
The purpose of this study was to investigate the effects of the D3 receptor partial agonist CJB 090 on the discriminative stimulus, reinforcing and priming effects of cocaine in squirrel monkeys. Complementary studies were conducted to compare CJB 090's effects on food-maintained behavior and species-typical unconditioned behaviors.
Monkeys were trained to: (1) discriminate cocaine from saline using a two-lever choice procedure, (2) self-administer cocaine on a second-order fixed-interval, fixed-ratio schedule of i.v. drug injection, or (3) self-administer food on a comparable second-order schedule of food delivery. A final group of monkeys served in quantitative observational studies of unconditioned behaviors.
In cocaine discrimination studies, pretreatment with CJB 090 significantly attenuated cocaine's discriminative stimulus effects. CJB 090 also significantly attenuated the partial cocaine-like stimulus effects of the preferential D3 receptor agonist PD 128907 but not the preferential D2 receptor agonist sumanirole. CJB 090 did not attenuate either self-administration of cocaine or cocaine-induced reinstatement of extinguished drug-seeking at a dose that reduced responding maintained by food. CJB 090 did not induce scratching or biting (species-typical effects of D2/3 receptor agonists) or catalepsy (typical effect of D2/3 receptor antagonists).
The results provide no evidence that CJB 090 reduced either the reinforcing or priming effects of cocaine but do suggest that CJB 090, acting via a D3 receptor mechanism, antagonized the discriminative stimulus effects of cocaine at a dose that did not induce adverse side effects.
多巴胺D3受体机制与可卡因的成瘾相关行为效应有关。
本研究旨在调查D3受体部分激动剂CJB 090对松鼠猴中可卡因的辨别刺激、强化和启动效应的影响。进行了补充研究以比较CJB 090对食物维持行为和物种典型非条件行为的影响。
猴子接受训练以：（1）使用双杠杆选择程序区分可卡因和生理盐水，（2）在静脉注射药物的二阶固定间隔、固定比率时间表上自我给药可卡因，或（3）在类似的食物递送二阶时间表上自我给药食物。最后一组猴子用于非条件行为的定量观察研究。
在可卡因辨别研究中，CJB 090预处理显著减弱了可卡因的辨别刺激效应。CJB 090还显著减弱了优先D3受体激动剂PD 128907的部分可卡因样刺激效应，但未减弱优先D2受体激动剂舒马尼罗的效应。在降低由食物维持的反应的剂量下，CJB 090既未减弱可卡因的自我给药，也未减弱可卡因诱导的消退的觅药行为恢复。CJB 090未诱导抓挠或咬（D2/3受体激动剂的物种典型效应）或僵住（D2/3受体拮抗剂的典型效应）。
结果没有提供证据表明CJB 090降低了可卡因的强化或启动效应，但确实表明CJB 090通过D3受体机制发挥作用，在不诱导不良副作用的剂量下拮抗了可卡因的辨别刺激效应。
