Incentive and dopamine sensitization produced by intermittent but not long access cocaine self-administration
Incentive and dopamine sensitization produced by intermittent but not long access cocaine self-administration
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DOI：
10.1111/ejn.14418
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发表时间：
2019-08-01
影响因子：
3.4
通讯作者：
Robinson, Terry E.
中科院分区：
文献类型：
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作者：
Kawa, Alex B.;Valenta, Alec C.;Robinson, Terry E.
药物使用的时间模式（药代动力学）对自我给药可卡因在啮齿动物中产生成瘾样行为和改变大脑的能力具有深远的影响。为了进一步解决这个问题，我们比较了长期接触（LgA）可卡因自我给药的影响，这被广泛用于模拟成瘾的过渡，间歇性接触（IntA），这被认为更好地反映了人类的药物使用模式，对单个，自我注射可卡因，以增加多巴胺（DA）溢出的核心，在脑桥核（使用体内微透析），并产生成瘾样行为。IntA的经验是更有效的比LGA在产生成瘾样行为的药物经验依赖性增加可卡因的动机评估使用行为经济学程序，和线索诱导的恢复，尽管少得多的总药物消费。透析液中DA的基础水平[DA]无组间差异，但在先前有IntA经验的大鼠中，单次自我给药IV注射可卡因在更大程度上增加了延髓核核心中的[DA]，而与LgA或有限进入经验的大鼠相比，后两组无差异。此外，可卡因的高动机与高[DA]反应相关。因此，IntA，而不是LGA，产生了激励和DA敏感。这与超反应多巴胺能系统可能有助于从偶然的药物使用模式过渡到定义成瘾的问题模式的概念一致。
The temporal pattern of drug use (pharmacokinetics) has a profound effect on the ability of self-administered cocaine to produce addiction-like behavior in rodents, and to change the brain. To further address this issue, we compared the effects of long access (LgA) cocaine self-administration, which is widely used to model the transition to addiction, with intermittent access (IntA), which is thought to better reflect the pattern of drug use in humans, on the ability of a single, self-administered injection of cocaine to increase dopamine (DA) overflow in the core of the nucleus accumbens (using in vivo microdialysis), and to produce addiction-like behavior. IntA experience was more effective than LgA in producing addiction-like behavior-a drug experience-dependent increase in motivation for cocaine assessed using behavioral economic procedures, and cue-induced reinstatement-despite much less total drug consumption. There were no group differences in basal levels of DA in dialysate [DA], but a single self-administered IV injection of cocaine increased [DA] in the core of the nucleus accumbens to a greater extent in rats with prior IntA experience than those with LgA or limited access experience, and the latter two groups did not differ. Furthermore, high motivation for cocaine was associated with a high [DA] response. Thus, IntA, but not LgA, produced both incentive and DA sensitization. This is consistent with the notion that a hyper-responsive dopaminergic system may contribute to the transition from casual patterns of drug use to the problematic patterns that define addiction.