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, Australia.
Int J Neuropsychopharmacol. 2011 Jun;14(5):684-90. doi: 10.1017/S1461145711000423. Epub 2011 Mar 29.
Orexinergic signalling is critical to drug relapse-like behaviour; however, the CNS sites(s) of action remain unknown. Two candidate brain regions are the paraventricular thalamus (PVT) and ventral tegmental area (VTA). We assessed the effect of intra-PVT or -VTA administration of the orexin-1 receptor (OrxR1) antagonist SB-334867 on discriminative cue-induced cocaine-seeking. Animals received either PVT- or VTA-directed SB-334867 (0, 3 or 6 μg; 0, 1 or 3 μg, respectively) prior to reinstatement testing elicited by presenting cocaine-paired stimuli (S+). The effect of VTA-directed injections of SB-334867 (0 or 3 μg) on locomotor activity was also assessed. Intra-VTA, but not -PVT, SB-334867 dose-dependently attenuated S+-induced reinstatement (3 μg dose, p<0.01). Intra-VTA SB-334867 had no effect on locomotor activity. We conclude that OrxR1 signalling within the VTA, but not the PVT, mediates cue-induced cocaine-seeking behaviour. We hypothesize that blockade of VTA OrxR1 signalling may reduce nucleus accumbens dopamine in response to drug cue presentation.
食欲素能信号对于药物复发性行为至关重要；然而，中枢神经系统的作用部位仍然未知。两个候选脑区是室旁丘脑（PVT）和腹侧被盖区（VTA）。我们评估了 PVT 或 VTA 内给予食欲素-1 受体（OrxR1）拮抗剂 SB-334867 对辨别线索诱导的可卡因寻求的影响。动物在可卡因配对刺激（S+）引起的重新激发测试之前接受 PVT 或 VTA 定向的 SB-334867（0、3 或 6μg；0、1 或 3μg，分别）。还评估了 VTA 定向注射 SB-334867（0 或 3μg）对运动活动的影响。VTA 内的 SB-334867 呈剂量依赖性地减弱了 S+诱导的重新激发（3μg 剂量，p<0.01）。VTA 内的 SB-334867 对运动活动没有影响。我们得出结论，VTA 内的 OrxR1 信号而不是 PVT 介导了线索诱导的可卡因寻求行为。我们假设 VTA OrxR1 信号的阻断可能会减少伏隔核多巴胺对药物线索呈现的反应。
