Czoty Paul W, Morgan Drake, Shannon Erin E, Gage H Donald, Nader Michael A
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1083, USA.
Psychopharmacology (Berl). 2004 Jul;174(3):381-8. doi: 10.1007/s00213-003-1752-z. Epub 2004 Feb 7.
Social rank has been shown to influence dopamine (DA) D(2) receptor function and vulnerability to cocaine self-administration in cynomolgus monkeys. The present studies were designed to extend these findings to maintenance of cocaine reinforcement and to DA D(1) receptors.
Examine the effects of a high-efficacy D(1) agonist on an unconditioned behavior (eyeblinking) and a low-efficacy D(1) agonist on cocaine self-administration, as well as the effects of cocaine exposure on D(2) receptor function across social ranks, as determined by positron emission tomography (PET).
Effects of the high-efficacy D(1) agonist SKF 81297 and cocaine (0.3-3.0 mg/kg) on spontaneous blinking were characterized in eight monkeys during 15-min observation periods. Next, the ability of the low-efficacy D(1) agonist SKF 38393 (0.1-17 mg/kg) to decrease cocaine self-administration (0.003-0.1 mg/kg per injection, IV) was assessed in 11 monkeys responding under a fixed-ratio 50 schedule. Finally, D(2) receptor levels in the caudate and putamen were assessed in nineteen monkeys using PET.
SKF 81297, but not cocaine, significantly increased blinking in all monkeys, with slightly greater potency in dominant monkeys. SKF 38393 dose-dependently decreased cocaine-maintained response rates with similar behavioral potency and efficacy across social rank. After an extensive cocaine self-administration history, D(2) receptor levels did not differ across social ranks.
These results suggest that D(1) receptor function is not substantially influenced by social rank in monkeys from well-established social groups. While an earlier study showed that dominant monkeys had higher D(2) receptor levels and were less sensitive to the reinforcing effects of cocaine during initial exposure, the present findings indicate that long-term cocaine use changed D(2) receptor levels such that D(2) receptor function and cocaine reinforcement were not different between social ranks. These findings suggest that cocaine exposure attenuated the impact of social housing on DA receptor function.
社会等级已被证明会影响食蟹猴体内多巴胺（DA）D2受体功能以及对可卡因自我给药的易感性。本研究旨在将这些发现扩展至可卡因强化维持以及DA D1受体方面。
研究高效D1激动剂对非条件行为（眨眼）的影响、低效D1激动剂对可卡因自我给药的影响，以及通过正电子发射断层扫描（PET）确定的可卡因暴露对不同社会等级D2受体功能的影响。
在15分钟的观察期内，对8只猴子进行高效D1激动剂SKF 81297和可卡因（0.3 - 3.0毫克/千克）对自发眨眼影响的研究。接下来，在11只按固定比率50程序做出反应的猴子中，评估低效D1激动剂SKF 38393（0.1 - 17毫克/千克）降低可卡因自我给药（静脉注射，每次注射0.003 - 0.1毫克/千克）的能力。最后，使用PET对19只猴子尾状核和壳核中的D2受体水平进行评估。
SKF 81297而非可卡因显著增加了所有猴子的眨眼次数，在优势猴中的效力略高。SKF 38393剂量依赖性地降低了可卡因维持的反应率，在不同社会等级中的行为效力和效果相似。在经历广泛的可卡因自我给药历史后，不同社会等级的D2受体水平并无差异。
这些结果表明，在已建立良好社会群体的猴子中，D1受体功能受社会等级的影响不大。虽然早期研究表明优势猴的D2受体水平较高，且在初次接触时对可卡因的强化作用不太敏感，但目前的研究结果表明，长期使用可卡因改变了D2受体水平，使得不同社会等级之间的D2受体功能和可卡因强化作用并无差异。这些发现表明，可卡因暴露减弱了群居环境对DA受体功能的影响。
