Abstract：
UNASSIGNED: The orexin (OX) system has received increasing interest as a potential target for treating substance use disorder. OX transmission in the posterior paraventricular nucleus of the thalamus (pPVT), an area activated by highly salient stimuli that are both reinforcing and aversive, mediates cue- and stress-induced reinstatement of reward-seeking behavior. Oral administration of suvorexant (SUV), a dual OX receptor (OXR) antagonist (DORA), selectively reduced conditioned reinstatement of oxycodone-seeking behavior and stress-induced reinstatement of alcohol-seeking behavior in dependent rats.
UNASSIGNED: This study tested whether OXR blockade in the pPVT with SUV reduces oxycodone or sweetened condensed milk (SCM) seeking elicited by conditioned cues or stress.
UNASSIGNED: Male Wistar rats were trained to self-administer oxycodone (0.15 mg/kg, i.v., 8 h/day) or SCM (0.1 ml, 2:1 dilution [v/v], 30 min/day). After extinction, we tested the ability of intra-pPVT SUV (15 µg/0.5 µl) to prevent reinstatement of oxycodone or SCM seeking elicited by conditioned cues or footshock stress.
UNASSIGNED: The rats acquired oxycodone and SCM self-administration, and oxycodone intake correlated with signs of physical opioid withdrawal, confirming dependence. Following extinction, the presentation of conditioned cues or footshock elicited reinstatement of oxycodone- and SCM-seeking behavior. Intra-pPVT SUV blocked stress-induced reinstatement of oxycodone seeking but not conditioned reinstatement of oxycodone or SCM seeking or stress-induced reinstatement of SCM seeking.
UNASSIGNED: The results indicate that OXR signaling in the pPVT is critical for stress-induced reinstatement of oxycodone seeking, further corroborating OXRs as treatment targets for opioid use disorder.
UNASSIGNED: This study tested whether OXR blockade in the pPVT with SUV reduces oxycodone or sweetened condensed milk (SCM) seeking elicited by conditioned cues or stress.
UNASSIGNED: Male Wistar rats were trained to self-administer oxycodone (0.15 mg/kg, i.v., 8 h/day) or SCM (0.1 ml, 2:1 dilution [v/v], 30 min/day). After extinction, we tested the ability of intra-pPVT SUV (15 µg/0.5 µl) to prevent reinstatement of oxycodone or SCM seeking elicited by conditioned cues or footshock stress.
UNASSIGNED: The rats acquired oxycodone and SCM self-administration, and oxycodone intake correlated with signs of physical opioid withdrawal, confirming dependence. Following extinction, the presentation of conditioned cues or footshock elicited reinstatement of oxycodone- and SCM-seeking behavior. Intra-pPVT SUV blocked stress-induced reinstatement of oxycodone seeking but not conditioned reinstatement of oxycodone or SCM seeking or stress-induced reinstatement of SCM seeking.
UNASSIGNED: The results indicate that OXR signaling in the pPVT is critical for stress-induced reinstatement of oxycodone seeking, further corroborating OXRs as treatment targets for opioid use disorder.
摘要：
■食欲素（OX）系统作为治疗物质使用障碍的潜在靶标受到越来越多的关注。丘脑室旁后核（pPVT）中的OX传递，由高度突出的刺激激活的区域，既增强又令人厌恶，调解线索和压力诱导的奖励寻求行为的恢复。口服suvorexant（SUV），双重OX受体（OXR）拮抗剂（DORA），在依赖性大鼠中选择性地减少了羟考酮寻求行为的条件恢复和应激诱导的酒精寻求行为的恢复。
■这项研究测试了使用SUV的pPVT中的OXR阻断是否减少了条件提示或压力引起的羟考酮或甜炼乳（SCM）寻求。
■雄性Wistar大鼠接受了自我服用羟考酮（0.15mg/kg，i.v.,8小时/天）或SCM（0.1毫升，2:1稀释[v/v]，30分钟/天)。灭绝之后,我们测试了pPVT内SUV（15µg/0.5µl）防止条件提示或脚部冲击压力引起的羟考酮或SCM寻求恢复的能力。
■大鼠获得了羟考酮和SCM自我给药，羟考酮的摄入量与阿片类药物戒断的迹象相关，确认依赖性。灭绝之后,条件性提示或脚部电击的出现引起了羟考酮和SCM寻求行为的恢复。pPVT内SUV阻止了压力诱导的羟考酮寻求的恢复，但没有调节羟考酮或SCM寻求的恢复或压力诱导的SCM寻求的恢复。
■结果表明，pPVT中的OXR信号传导对于应激诱导的羟考酮寻求的恢复至关重要，进一步证实OXR是阿片类药物使用障碍的治疗目标。
■这项研究测试了使用SUV的pPVT中的OXR阻断是否减少了条件提示或压力引起的羟考酮或甜炼乳（SCM）寻求。
■雄性Wistar大鼠接受了自我服用羟考酮（0.15mg/kg，i.v.,8小时/天）或SCM（0.1毫升，2:1稀释[v/v]，30分钟/天)。灭绝之后,我们测试了pPVT内SUV（15µg/0.5µl）防止条件提示或脚部冲击压力引起的羟考酮或SCM寻求恢复的能力。
■大鼠获得了羟考酮和SCM自我给药，羟考酮的摄入量与阿片类药物戒断的迹象相关，确认依赖性。灭绝之后,条件性提示或脚部电击的出现引起了羟考酮和SCM寻求行为的恢复。pPVT内SUV阻止了压力诱导的羟考酮寻求的恢复，但没有调节羟考酮或SCM寻求的恢复或压力诱导的SCM寻求的恢复。
■结果表明，pPVT中的OXR信号传导对于应激诱导的羟考酮寻求的恢复至关重要，进一步证实OXR是阿片类药物使用障碍的治疗目标。
