Cocaine- and amphetamine-regulated transcript (CART) signaling within the paraventricular thalamus modulates cocaine-seeking behaviour.
Cocaine- and amphetamine-regulated transcript (CART) signaling within the paraventricular thalamus modulates cocaine-seeking behaviour.
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DOI：
10.1371/journal.pone.0012980
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发表时间：
2010-09-23
期刊：
影响因子：
3.7
通讯作者：
Dayas CV
中科院分区：
文献类型：
--
作者：
James MH;Charnley JL;Jones E;Levi EM;Yeoh JW;Flynn JR;Smith DW;Dayas CV
可卡因和安非他明调节的转录本（CART）已被证明在调节各种滥用药物的奖励和强化效应中发挥作用。最近的一项研究表明，i. c. v. CART给药对酒精寻求的恢复有负面调节作用，然而，作用部位仍不清楚。我们研究了室旁丘脑（PVT）作为复发相关CART信号传导的潜在位点，因为已知该区域从含CART的下丘脑细胞接受密集的神经支配，并投射到已知参与介导恢复的许多区域，包括延髓核（NAC），内侧前额叶皮层（mPFC）和基底外侧杏仁核（BLA）。雄性大鼠被训练在被熄灭到设定的标准之前自我施用可卡因。灭绝后1天，动物接受生理盐水、河豚毒素（TTX; 2.5 ng）、CART（0.625 µg或2.5 µg）或不注射的PVT内输注，随后接受可卡因预充（10 mg/kg，i. p.）。然后在灭绝条件下对动物进行一小时的测试。使用TTX或CART治疗导致可卡因引发后的药物寻求行为显着减弱，2.5 μg剂量的CART具有最大的效果。这种效应对PVT区域是特异性的，因为TTX和CART的错误注射导致与对照相同的反应。我们第一次表明，PVT内的CART信号传导抑制药物引发的可卡因寻求行为的恢复，可能是通过负调节PVT传出，这对药物寻求是重要的，包括NAC，mPFC和BLA。通过这种方式，我们确定了一个可能的目标，为未来的药物干预，旨在抑制药物寻求。
Cocaine- and amphetamine-regulated transcript (CART) has been demonstrated to play a role in regulating the rewarding and reinforcing effects of various drugs of abuse. A recent study demonstrated that i.c.v. administration of CART negatively modulates reinstatement of alcohol seeking, however, the site(s) of action remains unclear. We investigated the paraventricular thalamus (PVT) as a potential site of relapse-relevant CART signaling, as this region is known to receive dense innervation from CART-containing hypothalamic cells and to project to a number of regions known to be involved in mediating reinstatement, including the nucleus accumbens (NAC), medial prefrontal cortex (mPFC) and basolateral amygdala (BLA). Male rats were trained to self-administer cocaine before being extinguished to a set criterion. One day following extinction, animals received intra-PVT infusions of saline, tetrodotoxin (TTX; 2.5 ng), CART (0.625 µg or 2.5 µg) or no injection, followed by a cocaine prime (10 mg/kg, i.p.). Animals were then tested under extinction conditions for one hour. Treatment with either TTX or CART resulted in a significant attenuation of drug-seeking behaviour following cocaine-prime, with the 2.5 µg dose of CART having the greatest effect. This effect was specific to the PVT region, as misplaced injections of both TTX and CART resulted in responding that was identical to controls. We show for the first time that CART signaling within the PVT acts to inhibit drug-primed reinstatement of cocaine seeking behaviour, presumably by negatively modulating PVT efferents that are important for drug seeking, including the NAC, mPFC and BLA. In this way, we identify a possible target for future pharmacological interventions designed to suppress drug seeking.
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DOI：
10.1124/jpet.105.091678
发表时间：
2005-12-01
影响因子：
3.5
作者：
Couceyro, PR;Evans, C;Bannon, AW
通讯作者：
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