Adolescents are more vulnerable to cocaine addiction: behavioral and electrophysiological evidence.
Adolescents are more vulnerable to cocaine addiction: behavioral and electrophysiological evidence.
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DOI：
10.1523/jneurosci.1371-12.2013
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发表时间：
2013-03-13
期刊：
影响因子：
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通讯作者：
Marinelli M
中科院分区：
文献类型：
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作者：
Wong WC;Ford KA;Pagels NE;McCutcheon JE;Marinelli M
在人类中，青春期是发展成可卡因成瘾的高度倾向时期。目前尚不清楚这是否归因于这个年龄段更多地接触和接触可卡因，或者青少年的大脑是否特别容易受到可卡因上瘾特性的影响。在这里，我们让雄性青春期(P42)和成年(~P88)大鼠接受广泛的可卡因自我给药程序。此外，为了确定行为差异是否与多巴胺能活动的发育差异有关，我们检查并操纵了多巴胺神经元的活动。与成年大鼠相比，青春期大鼠更容易服用可卡因，对低剂量更敏感，可卡因摄入量增加更多，更不容易受到价格上涨的影响(即更“缺乏弹性”)。同时，青少年还表现出腹侧被盖区多巴胺神经元的活动增加，这一特征被认为与自我管理行为的增加有关。使用奎比罗(激动剂)或乙氯必利(拮抗剂)对多巴胺D2受体功能进行药理学操作，以改变多巴胺神经元的活性，消除可卡因自身给药的年龄差异。这些数据表明，可卡因成瘾倾向的行为和电生理决定因素之间存在因果关系。总而言之，青少年表现出更高的成瘾倾向的行为和电生理特征。
In humans, adolescence is a period of heightened propensity to develop cocaine addiction. It is unknown whether this is attributable to greater access and exposure to cocaine at this age, or whether the adolescent brain is particularly vulnerable to the addictive properties of cocaine. Here, we subjected male adolescent (P42) and adult (~P88) rats to a wide range of cocaine self-administration procedures. In addition, to determine whether behavioral differences are associated with developmental differences in dopaminergic activity, we examined and manipulated the activity of dopamine neurons. Relative to adults, adolescent rats took cocaine more readily, were more sensitive to lower doses, showed greater escalation of cocaine intake, and were less susceptible to increases in price (i.e., were more “inelastic”). In parallel, adolescents also showed elevated activity of ventral tegmental area dopamine neurons, a feature known to be associated with increased self-administration behavior. Pharmacological manipulation of dopamine D2 receptor function with quinpirole (agonist) or eticlopride (antagonist), to alter dopamine neuron activity, eliminated age differences in cocaine self-administration. These data suggest a causal relationship between behavioral and electrophysiological determinants of cocaine addiction liability. In conclusion, adolescents show behavioral and electrophysiological traits of heightened addiction liability.