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首页> 外文期刊>Addiction biology >Increased relapse to cocaine‐seeking in a genetic model for depression
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Increased relapse to cocaine‐seeking in a genetic model for depression

机译：在抑郁症的遗传模型中寻找可卡因的复发增加

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Abstract The greatest difficulty in treating cocaine addiction is the enormous rates of relapse, which occur despite immense negative consequences. Relapse risks are even greater in addicts with comorbid depression, perhaps because they use drugs to alleviate depressive symptoms. Only a few preclinical studies have examined this comorbidity, mostly exploring depressive‐like effects following drug exposure. We examined rats from two different depression‐like models: (a) chronic‐mild‐stress (CMS), which respond to antidepressant medications and (b) depressed‐rat‐line (DRL), a genetic model of selective breeding, which is less responsive to antidepressant medications. We tested addictive behaviors in a cocaine self‐administration procedure, including the “conflict model , ” where drug ‐ seeking and relapse encounter adverse consequences: an electrified grid in front of the drug‐delivering lever. Following behavioral testing, we explored a potential association between behavioral outcomes and protein expression of brain‐derived neurotrophic factor (BDNF). We found that DRL rats self‐administer more cocaine compared with both CMS and controls, while CMS and control groups did not differ significantly. Notably, DRL but not CMS rats, displayed higher rates of relapse than controls, and expressed higher levels of BDNF in the prelimbic cortex (PLC). Potential translation of these results suggest that medication‐resistant depressed patients tend to consume more drugs and are more susceptible to relapse. The increase in PLC BDNF levels is consistent with previous rat models of depression, and concomitantly , with its suggested role in promoting cocaine‐seeking.
机译：摘要治疗可卡因成瘾的最大困难是巨大的复发率，尽管尽管存在巨大的负面影响。复发风险患者在瘾君子中甚至更大，具有可康抑郁症，也许是因为他们使用药物来缓解抑郁症状。只有少数临床前研究已经检查了这种合并症，主要探索了药物暴露后的抑郁症状。我们检查了来自两种不同抑郁症的大鼠的大鼠：（a）慢性轻度应激（CMS），其响应抗抑郁药物和（b）抑郁率 - 线（DRL），一种选择性育种的遗传模型，即选择性育种对抗抑郁药物的响应不太响应。我们在可卡因自我管理程序中测试了令人上瘾的行为，包括“冲突模型”，其中寻找和复发遭遇不良后果：药物输送杆前面的电网。行为测试后，我们探讨了脑衍生的神经营养因子（BDNF）的行为结果和蛋白质表达之间的潜在关系。我们发现DRL大鼠与CMS和对照组相比自我管理更多可卡因，而CMS和对照组没有显着差异。值得注意的是，DRL但不是CMS大鼠的复发率高于对照，并且在PRELIMBIC皮质（PLC）中表达了更高水平的BDNF。这些结果的潜在翻译表明，药物抗抑郁患者倾向于消耗更多的药物，并且更容易复发。 PLC BDNF水平的增加与之前的大鼠抑郁症模型一致，同时伴随着促进可卡因寻求的建议作用。

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