In vivo microdialysis reveals that blockade of accumbal orexin OX2 but not OX1 receptors enhances dopamine efflux in the nucleus accumbens of freely moving rats
In vivo microdialysis reveals that blockade of accumbal orexin OX2 but not OX1 receptors enhances dopamine efflux in the nucleus accumbens of freely moving rats
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DOI：
10.1111/ejn.15593
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发表时间：
2022-01-22
影响因子：
3.4
通讯作者：
Saigusa，Tadashi
中科院分区：
文献类型：
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作者：
Kawashima，Hiroki;Aono，Yuri;Saigusa，Tadashi
伏隔核含有食欲能神经输入和食欲素OX1‐和OX2‐受体。行为研究表明，伏隔进食素受体调节大鼠伏隔多巴胺能活动依赖的运动。我们利用体内微透析研究了在自由活动大鼠伏隔区注射食欲素受体配体对伏隔区细胞外多巴胺水平的影响，并分析了OX1‐和OX2‐受体在调节基底伏隔区多巴胺外排中的作用。食欲素受体配体通过附着透析探针的显微注射针在伏隔区内注射。非选择性OX1‐和OX2‐受体激动剂orexin‐A和选择性OX2‐受体激动剂orexin‐B （500.0 pg和5.0 ng）均未改变伏隔区多巴胺水平。非选择性OX1‐和OX2‐受体拮抗剂MK‐4305（过量，500.0 pg， 2.5和5.0 ng）增强多巴胺外排。将河豚毒素注入伏隔核2小时，通过探测或共同给药食欲素A (500.0 pg)，可以强烈抑制MK - 4305 （5.0 ng）诱导的伏隔核多巴胺外排。选择性OX2受体拮抗剂EMPA（90.0和900.0 pg, 9.0 ng）增加多巴胺外排。伏核内输注河豚毒素可消除EMPA （9.0 ng）诱导的多巴胺外排。选择性OX1‐受体拮抗剂SB‐334867（10.0和20.0 ng）未能改变多巴胺外排。同时给药orexin - B （500.0 pg）抑制EMPA （9.0 ng）‐和MK - 4305 （5.0 ng）‐诱导的多巴胺外排。腹腔注射MK - 4305 （10.0 mg/kg）不影响伏隔区多巴胺外排。本研究提供了体内神经药理学证据，表明伏隔区OX2‐而不是OX1‐受体对伏隔区基底多巴胺外排起抑制调节作用，并且阻断伏隔区OX2‐受体可增强自由活动大鼠伏隔核的多巴胺外排。
The nucleus accumbens contain orexinergic neural inputs and orexin OX1‐ and OX2‐receptors. Behavioural studies suggest that accumbal orexin receptors modulate accumbal dopaminergic activity‐dependent locomotion in rats. We studied the effects of intra‐accumbal injection of orexin receptor ligands on accumbal extracellular dopamine levels in freely moving rats, usingin vivomicrodialysis and analysed the roles of OX1‐ and OX2‐receptors in the regulation of basal accumbal dopamine efflux. The orexin receptor ligands were applied intra‐accumbally though a microinjection needle attached with a dialysis probe. Neither the nonselective OX1‐ and OX2‐receptor agonist orexin‐A nor the preferential OX2‐receptor agonist orexin‐B (500.0 pg and 5.0 ng) altered accumbal dopamine levels. The nonselective OX1‐ and OX2‐receptor antagonist MK‐4305 (suvorexant, 500.0 pg, 2.5 and 5.0 ng) enhanced dopamine efflux. A 2‐h tetrodotoxin infusion into nucleus accumbens through the probe or co‐administration of orexin‐A (500.0 pg) strongly inhibited MK‐4305 (5.0 ng)‐induced accumbal dopamine efflux. The selective OX2‐receptor antagonist EMPA (90.0 and 900.0 pg, 9.0 ng) increased dopamine efflux. Intra‐accumbal infusion of tetrodotoxin abolished EMPA (9.0 ng)‐induced dopamine efflux. The selective OX1‐receptor antagonist SB‐334867 (10.0 and 20.0 ng) failed to alter dopamine efflux. Co‐administration of orexin‐B (500.0 pg) inhibited both EMPA (9.0 ng)‐ and MK‐4305 (5.0 ng)‐induced dopamine efflux. Intraperitoneal injection of MK‐4305 (10.0 mg/kg) did not affect accumbal dopamine efflux. The present study providesin vivoneuropharmacological evidence that accumbal OX2‐ but not OX1‐receptors exert inhibitory regulation of basal accumbal dopamine efflux and that blockade of accumbal OX2‐receptors enhances dopamine efflux in nucleus accumbens of freely moving rats.