Individual differences in dopamine cell neuroadaptations following cocaine self-administration.
Individual differences in dopamine cell neuroadaptations following cocaine self-administration.
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DOI：
10.1016/j.biopsych.2009.04.018
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发表时间：
2009-10-15
影响因子：
10.6
通讯作者：
Marinelli, Michela
中科院分区：
文献类型：
--
作者：
McCutcheon, James E.;White, Francis J.;Marinelli, Michela
成瘾性药物在腹侧被盖区（VTA）多巴胺神经元中产生神经适应性。目前尚不清楚这些神经适应性反应的个体差异是否可以解释自然发生的药物成瘾倾向差异。为了研究这个问题，我们利用了高反应和低反应（HR和LR）大鼠，这是一个在几种成瘾模型中表现出自发差异的种群。HR和LR大鼠被允许在短时间内自行给药生理盐水或高剂量可卡因（500 μg/kg/输注），以使个体间的药物摄入正常化。在不同的停药期后，记录药物引起的VTA多巴胺神经元基线活动的变化。所有大鼠都表现出自我给药行为，并显示出相似的药物摄入量。在所有动物中，戒断可卡因会增加多巴胺细胞的放电和爆裂。然而，这些放电速率和模式的变化在hrr大鼠中比在LR大鼠中更持久。这些结果证明了药物诱导的VTA多巴胺神经元神经适应持续时间的个体差异。多巴胺细胞活性的持续升高和恢复到基线水平的能力的降低可能是导致“高危”个体成瘾的重要因素。
Addictive drugs produce neuroadaptations in dopamine neurons of the ventral tegmental area (VTA). It is unknown if individual differences in these neuroadaptive responses can account for naturally-occurring differences in drug addiction liability. To study this question, we took advantage of high- and low-responder (HR and LR) rats, a population that exhibits spontaneous differences in several models of addiction. HR and LR rats were allowed to self-administer saline or a high dose of cocaine (500 μg/kg/infusion) over a brief period, to normalize drug intake across individuals. Drug-induced changes in the baseline activity of VTA dopamine neurons were recorded after various periods of withdrawal. All rats developed self-administration behavior and showed similar levels of drug intake. Withdrawal from cocaine self-administration increased dopamine cell firing and bursting in all animals. However these changes in firing rates and patterns were more persistent in HRthan in LR rats. These results demonstrate individual differences in the duration of drug-induced neuroadaptations in dopamine neurons of the VTA. More persistent elevation of dopamine cell activity and reduced capacity to return to baseline levels may be an important factor contributing to the development of addiction in “at risk” individuals.
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影响因子：
4.2
作者：
Stoffel, Erin C.;Cunningham, Kathryn A.
通讯作者：
Cunningham, Kathryn A.
影响因子：
8.2
作者：
Vezina, P
通讯作者：
Vezina, P
影响因子：
3
作者：
Marinelli, M.;Rudick, C. N.;White, F. J.
通讯作者：
White, F. J.
影响因子：
5.3
作者：
Lodge, Daniel J.;Grace, Anthony A.
通讯作者：
Grace, Anthony A.
可卡因，但不是自然奖励自我给药或被动可卡因输注在VTA中产生持久的LTP。
影响因子：
16.2
作者：
Chen BT;Bowers MS;Martin M;Hopf FW;Guillory AM;Carelli RM;Chou JK;Bonci A
通讯作者：
Bonci A