引用

戒断药物自我管理后，重新吸食甲基苯丙胺(冰毒渴望的潜伏期)，并逐渐增加。我们之前证明了背内侧纹状体(DMS)多巴胺D1受体(D1Rs)在这种孵育中的作用。在这里，我们研究了传入谷氨酸投射到DMS和局部d1r -谷氨酸相互作用在雄性大鼠孵育中的作用。在第30天复发试验中，我们首先在投射区使用CTb(逆行示踪剂)+ Fos(活性标记物)双标记来测量投射特异性激活。接下来，我们确定了在停药第30天，丘脑外侧或内侧板内前核(AIT-L或AIT-M)的药理学可逆失活对孵育冰毒寻求的影响。然后，我们使用解剖学上的不对称断开程序来确定AIT-LDMS谷氨酸投射和突触后DMS D1Rs之间的相互作用是否有助于孵育的冰毒寻求。我们还确定了AIT-L的单侧失活和DMS的D1Rs封锁对孵化的冰毒寻求的影响，以及AIT-LDMS对侧断开投射对停药第1天非孵化的冰毒寻求的影响。潜伏性冰毒寻求与AITDMS投射的选择性激活相关;其他到DMS的谷氨酸投射未被激活。AIT-L(但不包括AIT-M)失活或AIT-LDMS投影的解剖断开降低了孵育的Meth寻求。AIT-L的单侧失活或DMS的D1Rs阻断对酝酿的冰毒渴望没有影响，AIT-LDMS的对侧断开对非酝酿的冰毒寻求没有影响。我们的研究结果确定了AIT-L和AIT-LDMS谷氨酸投射在药物渴望和药物寻求的潜伏期中的新作用。SIGNIFICANCE STATEMENTMethamphetamine seeking progressively increases after withdrawal from drug self-administration, a phenomenon termed incubation of methamphetamine craving. We previously found that D1R-mediated dopamine transmission in dorsomedial striatum plays a critical role in this incubation phenomenon. Here, we used neuroanatomical and neuropharmacological methods in rats to demonstrate that an interaction between the glutamatergic projection from the lateral anterior intralaminar nuclei of thalamus to dorsomedial striatum and local dopamine D1Rs plays a critical role in relapse to methamphetamine seeking after prolonged withdrawal. Our study identified a novel motivation-related thalamostriatal projection that is critical to relapse to drug seeking.