Chemogenetic inhibition of the bed nucleus of the stria terminalis suppresses the intake of a preferable and learned aversive sweet taste solution in male mice
Chemogenetic inhibition of the bed nucleus of the stria terminalis suppresses the intake of a preferable and learned aversive sweet taste solution in male mice
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DOI：
10.1016/j.bbr.2022.114253
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发表时间：
2022-12-13
影响因子：
2.7
通讯作者：
Funahashi，Makoto
中科院分区：
文献类型：
--
作者：
Kikuchi，Emi;Inui，Tadashi;Funahashi，Makoto
条件味觉厌恶（CTA）是通过将味觉溶液作为条件刺激（CS）与内脏不适作为非条件刺激（US）配对而建立的。CTA降低了CS的口感适口性。终纹床核接收来自脑干的味觉输入。然而，BNST在CTA中的作用尚不清楚。因此，本研究考察了CTA获取后BNST神经元的化学发生抑制对CS摄入的影响。将一种腺相关病毒微注射到雄性C57/BL6小鼠的BNST中，诱导抑制设计器受体hM4Di。小鼠接受0.2%糖精溶液（CS）与0.3 M氯化锂（2%体重，腹腔）配对。调节后，给予氯氮平- n -氧化物（CNO, 1 mg/kg）与生理盐水相比，显著增强了CS摄入对CTA回收的抑制作用（p < 0.01）。我们进一步评估了BNST神经元抑制对水和味觉溶液（糖精、三氯蔗糖、氯化钠、味精、盐酸奎宁和柠檬酸）摄入的影响，使用naïve（未习得CTA）小鼠。CNO显著降低了糖精和三氯蔗糖的摄取量（p < 0.05）。我们的研究结果表明，BNST神经元介导甜味并调节甜味摄入，而不管甜食是应该被摄入还是被拒绝。BNST神经元可能在CTA的检索中受到抑制，从而抑制了CS的摄入。
Conditioned taste aversion (CTA) is established by pairing a taste solution as a conditioned stimulus (CS) with visceral malaise as an unconditioned stimulus (US). CTA decreases the taste palatability of a CS. The bed nucleus of the stria terminalis (BNST) receives taste inputs from the brainstem. However, the involvement of the BNST in CTA remains unclear. Thus, this study examined the effects of chemogenetic inhibition of the BNST neurons on CS intake after CTA acquisition. An adeno-associated virus was microinjected into the BNST of male C57/BL6 mice to induce the inhibitory designer receptor hM4Di. The mice received a pairing of 0.2% saccharin solution (CS) with 0.3 M lithium chloride (2% BW, intraperitoneal). After conditioning, the administration of clozapine–N–oxide (CNO, 1 mg/kg) significantly enhanced the suppression of CS intake on the retrieval of CTA compared with its intake following saline administration (p < 0.01). We further assessed the effect of BNST neuron inhibition on the intake of water and taste solutions (saccharin, sucralose, sodium chloride, monosodium glutamate, quinine hydrochloride, and citric acid) using naïve (not learned CTA) mice. CNO administration significantly decreased the intake of saccharin and sucralose (p < 0.05). Our results indicate that BNST neurons mediate sweet taste and regulate sweet intake, regardless of whether sweets should be ingested or rejected. BNST neurons may be inhibited in the retrieval of CTA, thereby suppressing CS intake.