Double dissociation of the dorsomedial and dorsolateral striatal control over the acquisition and performance of cocaine seeking.
Double dissociation of the dorsomedial and dorsolateral striatal control over the acquisition and performance of cocaine seeking.
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DOI：
10.1038/npp.2012.104
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发表时间：
2012-10
期刊：
影响因子：
--
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中科院分区：
文献类型：
--
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本研究探讨了前背外侧(ADLS)和后背内侧(PDMS)纹状体的多巴胺依赖机制在可卡因寻找行为的早期和晚期表现中的作用。训练大鼠在持续强化(固定比率1)下自我给予可卡因，每次注射时给予20-S光条件刺激(CS)。一周后，在不受可卡因影响的15分钟内，大鼠接受应变变化的挑战，寻找可卡因，在此期间，1-S CS演示强化了每个反应。脑内注射α-flupenthixol可阻断多巴胺的传递，但不阻断ADL的多巴胺传递，剂量依赖性地降低自身给药早期线索控制的可卡因寻找能力。然后，一组大鼠接受了增加反应要求的训练，直到按照二级时间表完成15次训练[FI15(FR10：S)]，以便很好地建立寻找可卡因的能力。在此阶段，α-flupenthixol内注射ADLS，而不是PDMS，可剂量依赖性地减少主动杠杆按压。第二组大鼠继续在FR1时间表下自我注射可卡因，以便它们的药物摄入量与晚期表现组相匹配。α-flupenthixol在PDMS中，但不在ADLS中，再次阻止了可卡因寻找的表现。这些结果表明，PDMS中的多巴胺传递是目标导向型可卡因寻找的初始行为所必需的，其作用最终被颠覆，只有在高可卡因寻找行为发生率的训练后才移交给ADLS，这支持纹状体对可卡因寻找的控制在目标导向型和习惯性行为之间的动态变化的理论。
The present study investigated the involvement of dopamine-dependent mechanisms in the anterior dorsolateral (aDLS) and posterior dorsomedial (pDMS) striatum during the early- and late-stage performance of cocaine-seeking behavior. Rats were trained to self-administer cocaine under continuous reinforcement (fixed-ratio 1, FR1) with a 20-s light conditioned stimulus (CS) presented contingently upon each infusion. After a week, rats were challenged by a change in contingency to seek cocaine during a 15-min period uninfluenced by cocaine during which each response was reinforced by a 1-s CS presentation. Dopamine transmission blockade by intracranial infusions of α-flupenthixol only in the pDMS, but not in the aDLS, dose dependently reduced performance of cue-controlled cocaine seeking at the early stage of self-administration. One cohort of rats was then trained with increasing response requirements until completing 15 sessions under a second-order schedule [FI15(FR10:S)] so that cocaine-seeking performance became well established. At this stage, intra-aDLS, but not pDMS, α-flupenthixol infusions dose dependently reduced active lever presses. The second cohort of rats continued to self-administer cocaine under the FR1 schedule such that their drug intake was matched to the late-stage performance group. α-Flupenthixol in the pDMS, but not in the aDLS, again prevented the performance of cocaine seeking. These results show that dopamine transmission in the pDMS is required for initial performance of goal-directed cocaine seeking, and that its role is ultimately subverted and devolves instead to the aDLS only following training with high rates of cocaine-seeking behavior, supporting the theory of dynamic shifts in the striatal control over cocaine seeking between goal-directed and habitual performance.
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影响因子：
3.7
作者：
Lex, Bjoern;Hauber, Wolfgang
通讯作者：
Hauber, Wolfgang
DOI：
10.1080/14640748108400816
发表时间：
1981-01-01
期刊：
QUARTERLY JOURNAL OF EXPERIMENTAL PSYCHOLOGY SECTION B-COMPARATIVE AND PHYSIOLOGICAL PSYCHOLOGY
影响因子：
--
作者：
ADAMS, CD;DICKINSON, A
通讯作者：
DICKINSON, A
影响因子：
3.3
作者：
KELLEY, AE;DOMESICK, VB;NAUTA, WJH
通讯作者：
NAUTA, WJH
影响因子：
25
作者：
Ito, R;Robbins, TW;Everitt, BJ
通讯作者：
Everitt, BJ
影响因子：
3.4
作者：
Murray, Jennifer E.;Everitt, Barry J.;Belin, David
通讯作者：
Belin, David