Lack of Causal Roles of Cannabinoid and Dopamine Neurotransmitter Systems in Orbitofrontal and Piriform Cortex in Fentanyl Relapse in Rats.
Lack of Causal Roles of Cannabinoid and Dopamine Neurotransmitter Systems in Orbitofrontal and Piriform Cortex in Fentanyl Relapse in Rats.
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DOI：
10.1523/eneuro.0496-21.2022
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发表时间：
2022-07-01
期刊：
影响因子：
3.4
通讯作者：
Reiner, David J
中科院分区：
文献类型：
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作者：
Claypool, Sarah M;Behdin, Sana;Reiner, David J
眶额皮质（OFC）和梨状皮质（Pir）在食物选择诱导的自愿禁欲后芬太尼复发中发挥作用，这是一种模仿禁欲的过程，因为可以获得替代的非药物奖励。我们使用原位杂交和药理学来确定OFC和Pir大麻素和多巴胺受体在芬太尼复发中的作用。我们训练雄性和雌性大鼠自我给药食物颗粒6d（6 h/d）和静脉注射芬太尼（2.5g/kg/输液）12 d（6 h/d）。我们评估了芬太尼和食物之间的12个离散的选择会议（20次试验/天），其中大鼠自愿减少芬太尼自我管理后，芬太尼复发。我们使用RNAscope来确定芬太尼复发是否与表达Cnr 1（编码大麻素1（CB 1）受体）或Drd 1和Drd 2（编码多巴胺D1和D2受体）的OFC和Pir细胞中的活性（由Fos表示）相关。我们将CB_1受体拮抗剂或激动剂（0.3或1.0gAM_（251）或WIN 55，212-2/半球）注入OFC或多巴胺D_1受体拮抗剂（1.0或3.0gSCH_（39166）/半球）注入Pir以确定对芬太尼复发的影响。芬太尼复发与OFC细胞共表达Fos和Cnr 1以及Pir细胞共表达Fos和Drd 1相关。然而，向OFC中注射CB 1受体拮抗剂AM 251或激动剂WIN 55，212-2或向Pir中注射多巴胺D1受体拮抗剂SCH 39166对芬太尼复发没有影响。芬太尼复发与表达Cnr 1的OFC细胞和表达Drd 1的Pir细胞的激活有关，但药理学操作不支持OFC CB 1受体或Pir多巴胺D1受体在芬太尼复发中的因果作用。
The orbitofrontal cortex (OFC) and piriform cortex (Pir) play a role in fentanyl relapse after food choice-induced voluntary abstinence, a procedure mimicking abstinence because of availability of alternative nondrug rewards. We used in situ hybridization and pharmacology to determine the role of OFC and Pir cannabinoid and dopamine receptors in fentanyl relapse. We trained male and female rats to self-administer food pellets for 6d (6 h/d) and intravenous fentanyl (2.5g/kg/infusion) for 12d (6 h/d). We assessed fentanyl relapse after 12 discrete choice sessions between fentanyl and food (20 trials/d), in which rats voluntarily reduced fentanyl self-administration. We used RNAscope to determine whether fentanyl relapse is associated with activity (indicated by Fos) in OFC and Pir cells expressing Cnr1 [which encodes cannabinoid 1 (CB1) receptors] or Drd1 and Drd2 (which encode dopamine D1 and D2 receptors). We injected a CB1 receptor antagonist or agonist (0.3 or 1.0g AM251 or WIN55,212-2/hemisphere) into OFC or a dopamine D1 receptor antagonist (1.0 or 3.0g SCH39166/hemisphere) into Pir to determine the effect on fentanyl relapse. Fentanyl relapse was associated with OFC cells co-expressing Fos and Cnr1 and Pir cells co-expressing Fos and Drd1 However, injections of the CB1 receptor antagonist AM251 or agonist WIN55,212-2 into OFC or the dopamine D1 receptor antagonist SCH39166 into Pir had no effect on fentanyl relapse. Fentanyl relapse is associated with activation of Cnr1-expressing OFC cells and Drd1-expressing Pir cells, but pharmacological manipulations do not support causal roles of OFC CB1 receptors or Pir dopamine D1 receptors in fentanyl relapse.