Neurobiology of Addiction Laboratory, School of Biomedical Sciences and Pharmacy and the Centre for Brain and Mental Health Research, University of Newcastle and the Hunter Medical Research Institute, Newcastle, NSW 2038, Australia.
Neuroscience. 2011 Dec 29;199:235-42. doi: 10.1016/j.neuroscience.2011.09.047. Epub 2011 Sep 28.
The thalamus is considered an important interface between the ventral striatopallidum and the dorsal striatum, and may therefore contribute to compulsive drug-seeking behaviour. Recent evidence suggests that the paraventricular thalamus (PVT), a dorsal midline thalamic nucleus, and the mediodorsal thalamus (MD) are involved in drug self-administration and respond to drug-associated cues. At present, however, the role of these thalamic regions in mediating cue-induced reinstatement of cocaine-seeking is unclear. Similarly, the habenula complex, part of the epithalamus, has been implicated in nicotine self-administration and cue-induced reinstatement of heroin seeking, but the role of this region in cocaine reinstatement behaviour has received little attention. Rats (n=20) were trained to self-administer cocaine in the presence of discriminative stimuli associated with drug availability (S⁺) or drug non-availability (S⁻). Once a stable level of responding was reached, lever pressing was extinguished. Animals were then tested for reinstatement and sacrificed immediately following the presentation of either the S⁻ or S⁺ discriminative stimuli, and Fos-protein expression was assessed in thalamic and epithalamic regions. Interestingly, significant variation was observed in reinstatement behaviour, allowing a comparison between high-reinstating (HR), low-reinstating (LR) and control animals. Compared with LR animals, HR animals exhibited increased Fos-protein expression in the PVT, intermediodorsal thalamus and the medial and lateral divisions of the habenula. Our data provide evidence that activation of thalamic and epithalamic nuclei is associated with propensity to reinstate to cocaine-seeking elicited by drug-related cues. We also build upon existing data highlighting the importance of the PVT in reinstatement behaviour.
丘脑被认为是腹侧纹状体-苍白球和背侧纹状体之间的重要接口，因此可能有助于强迫性觅药行为。最近的证据表明，室旁丘脑（PVT），一个背中线丘脑核，和中背侧丘脑（MD）参与药物自我给药，并对药物相关线索作出反应。然而，目前这些丘脑区域在介导线索诱导的可卡因寻求复发起作用尚不清楚。同样，缰核复合体，即上丘脑的一部分，已被牵连到尼古丁的自我给药和海洛因寻求的线索诱导复发起作用，但该区域在可卡因复发起作用中的作用受到的关注较少。大鼠（n=20）接受可卡因自我给药训练，同时存在与药物可用性（S⁺）或药物不可用（S⁻）相关的辨别刺激。一旦达到稳定的反应水平，就会熄灭压杆。然后对动物进行复发起诉测试，并在呈现 S⁻或 S⁺辨别刺激后立即处死，评估丘脑和上丘脑区域的 Fos-蛋白表达。有趣的是，观察到复发起诉行为存在显著差异，允许对高复发起诉（HR）、低复发起诉（LR）和对照动物进行比较。与 LR 动物相比，HR 动物在 PVT、中背侧丘脑以及缰核的内侧和外侧部分的 Fos-蛋白表达增加。我们的数据提供了证据，表明激活丘脑和上丘脑核与药物相关线索引起的可卡因寻求复发起诉的倾向有关。我们还基于现有数据强调了 PVT 在复发起诉行为中的重要性。
