Department of Pharmacology, Laboratory of Neuroanatomy and Neuropsychobiology, Ribeirão Preto Medical School of the University of São Paulo, Ribeirão Preto, São Paulo, Brasil.
NAP-USP-Neurobiology of Emotions Research Centre, Ribeirão Preto Medical School of the University of São Paulo, Ribeirão Preto, São Paulo, Brasil.
J Psychopharmacol. 2021 Jan;35(1):78-90. doi: 10.1177/0269881120967881. Epub 2020 Dec 10.
Previous studies suggested that Cg1 area of the cingulate cortex of rats controls glutamate-mediated fear-induced defensive behaviour and antinociception organised at the posterior hypothalamus. In turn, microinjection of the nitric oxide donor SIN-1 into the anterior hypothalamus of mice produced defensive behaviours and fear-induced antinociception. However, it remains unknown whether Cg1 also modulates the latter mechanisms in mice.
The present study examined the influence of Cg1 on SIN1-evoked fear-induced defensive behaviour and antinociception organised at the anterior hypothalamus of mice.
The fear-like behavioural and antinociceptive responses to the microinjection of SIN-1 (300 nmol) into the anterior hypothalamus were evaluated after the microinjection of either N-methyl-D-aspartic acid receptor agonist (0.1, 1 and 10 nmol) or physiological saline into the cingulate cortex of C57BL/6 male mice. In addition, neurotracing and immunohistochemistry were used to characterise Cg1-anterior hypothalamus glutamatergic pathways.
The data showed that activation of Cg1 N-methyl-D-aspartic acid receptors increased escape while reducing freezing and antinociceptive responses to SIN-1 microinjections into the anterior hypothalamus. Anterograde neural tract tracer co-localised with VGLUT2-labelled fibres suggests these responses are mediated by glutamatergic synapses at the anterior hypothalamus.
In contrast with previous studies showing that Cg1 facilitates both escape and antinociception to chemical stimulation of the posterior hypothalamus in rats, the present data suggest that Cg1 facilitates escape while inhibiting defensive antinociception produced by the microinjection of SIN-1 in the anterior hypothalamus of mice. Accordingly, Cg1 may have opposite effects on antinociceptive responses organised in the anterior and posterior hypothalamus of mice and rats, respectively.
先前的研究表明，大鼠扣带皮层 Cg1 区控制谷氨酸介导的恐惧诱导防御行为和在后丘脑组织的镇痛作用。相反，一氧化氮供体 SIN-1 在前脑丘脑中的微量注射会产生防御行为和恐惧诱导的镇痛作用。然而，Cg1 是否也调节小鼠的后一种机制尚不清楚。
本研究检查了 Cg1 对 SIN1 诱发的恐惧诱导防御行为和在前脑丘脑中组织的镇痛作用的影响。
在 C57BL/6 雄性小鼠的扣带皮层中注射 N-甲基-D-天冬氨酸受体激动剂（0.1、1 和 10nmol）或生理盐水后，评估 SIN-1（300nmol）在前脑丘脑中微量注射引起的类似恐惧的行为和镇痛反应。此外，还使用神经示踪剂和免疫组织化学来描述 Cg1-前脑丘脑中的谷氨酸能通路。
数据显示，Cg1 N-甲基-D-天冬氨酸受体的激活增加了逃避行为，同时减少了对 SIN-1 在前脑丘脑中微量注射的冻结和镇痛反应。顺行神经束示踪剂与 VGLUT2 标记纤维共定位表明，这些反应是由前脑丘脑中的谷氨酸能突触介导的。
与先前的研究表明 Cg1 促进大鼠后丘脑化学刺激的逃避和镇痛作用相反，本研究数据表明，Cg1 促进逃避行为，同时抑制 SIN-1 在前脑丘脑中微量注射产生的防御性镇痛作用。因此，Cg1 可能对小鼠和大鼠前脑和后脑丘脑中的镇痛反应产生相反的影响。
