Gould Robert W, Czoty Paul W, Porrino Linda J, Nader Michael A
Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Department of Radiology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Neuropsychopharmacology. 2017 Apr;42(5):1093-1102. doi: 10.1038/npp.2016.285. Epub 2016 Dec 27.
Individual differences in response to social stress and environmental enrichment may contribute to variability in response to behavioral and pharmacological treatments for drug addiction. In monkeys, social status influences the reinforcing effects of cocaine and the effects of some drugs on cocaine self-administration. In this study, we used male cynomolgus macaques (n=15) living in established social groups to examine the effects of social confrontation on the reinforcing effects of cocaine using a food-drug choice procedure. On the test day, a dominant or subordinate monkey was removed from his homecage and placed into another social pen; 30 min later he was studied in a cocaine-food choice paradigm. For the group, following social confrontation, sensitivity to cocaine reinforcement was significantly greater in subordinate monkeys compared with dominant animals. Examining individual-subject data revealed that for the majority of monkeys (9/15), serving as an intruder in another social group affected cocaine self-administration and these effects were dependent on the social rank of the monkey. For subordinate monkeys, sensitivity to the reinforcing effects of cocaine increased while sensitivity decreased in dominant monkeys. To investigate potential mechanisms mediating these effects, brain glucose metabolism was studied in a subset of monkeys (n=8) using [F]fluorodeoxyglucose ([F]FDG) with positron emission tomography. Dominant and subordinate monkeys displayed distinctly different patterns of brain glucose metabolism in their homecage, including areas associated with vigilance and stress/anxiety, respectively, and during social confrontation. These data demonstrate that, depending on an individual's social status, the same social experience can have divergent effects on brain function and cocaine self-administration. These phenotypic differences in response to social conditions support a personalized treatment approach to cocaine addiction.
对社会压力和环境丰富化的反应存在个体差异，这可能导致对药物成瘾的行为和药物治疗反应出现变异性。在猴子中，社会地位会影响可卡因的强化作用以及某些药物对可卡因自我给药的影响。在本研究中，我们使用生活在既定社会群体中的雄性食蟹猴（n = 15），通过食物 - 药物选择程序来研究社会对抗对可卡因强化作用的影响。在测试日，将一只优势或从属猴子从其笼舍中移出并放入另一个社交围栏；30分钟后，在可卡因 - 食物选择范式中对其进行研究。对于整个群体而言，社会对抗后，从属猴子对可卡因强化作用的敏感性显著高于优势动物。检查个体数据发现，对于大多数猴子（9/15）来说，作为另一个社会群体中的入侵者会影响可卡因自我给药，且这些影响取决于猴子的社会等级。对于从属猴子，对可卡因强化作用的敏感性增加，而优势猴子的敏感性降低。为了研究介导这些影响的潜在机制，我们使用[F]氟脱氧葡萄糖（[F]FDG）和正电子发射断层扫描技术，在一部分猴子（n = 8）中研究了脑葡萄糖代谢。优势和从属猴子在其笼舍中以及社会对抗期间，显示出明显不同的脑葡萄糖代谢模式，分别包括与警觉和应激/焦虑相关的区域。这些数据表明，取决于个体的社会地位，相同的社会经历对脑功能和可卡因自我给药可能产生不同的影响。这些对社会条件反应的表型差异支持针对可卡因成瘾的个性化治疗方法。
