Madden C J, Morrison S F
Neurological Sciences Institute, Oregon Health and Science University, 505 NW 185th Avenue, Beaverton, OR 97006, USA.
Neuropharmacology. 2008 Mar;54(3):487-96. doi: 10.1016/j.neuropharm.2007.10.019. Epub 2007 Nov 5.
In urethane-chloralose anesthetized, neuromuscularly blocked, ventilated rats, microinjection of NMDA (12 pmol) into the right fourth thoracic segment (T4) spinal intermediolateral nucleus (IML) immediately increased ipsilateral brown adipose tissue (BAT) sympathetic nerve activity (SNA; peak +492% of control), expired CO2 (+0.1%) heart rate (+48 beats min(-1)) and arterial pressure (+8 mmHg). The increase in BAT SNA evoked by T4 IML microinjection of NMDA was potentiated when it was administered immediately following a T4 IML microinjection of 5-hydroxytryptamine (5-HT, 100 pmol) or the 5-HT1A/5-HT7 receptor agonist, 8-OH-DPAT (600 pmol), (area under the curve: 184%, and 259% of the NMDA-only response, respectively). In contrast, T4 IML microinjection of the 5-HT2 receptor agonist, DOI (28 pmol) did not potentiate the NMDA-evoked increase in BAT SNA (101% of NMDA-only response). Microinjection into the T4 IML of the selective 5-HT1A antagonist, WAY-100635 (500 pmol), plus the 5-HT7 antagonist, SB-269970 (500 pmol), prevented the 5-HT-induced potentiation of the NMDA-evoked increase in BAT SNA. When administered separately, WAY-100635 (800 pmol) and SB-269970 (800 pmol) attenuated the 8-OH-DPAT-induced potentiation of the NMDA-evoked increase in BAT SNA through effects on the amplitude and duration of the response, respectively. The selective 5-HT2 receptor antagonist, ketanserin (100 pmol), did not attenuate the potentiations of the NMDA-evoked increase in BAT SNA induced by either 5-HT or 8-OH-DPAT. These results demonstrate that activation of 5-HT1A/5-HT7 receptors can act synergistically with NMDA receptor activation within the IML to markedly increase BAT SNA.
在氨基甲酸乙酯 - 氯醛糖麻醉、神经肌肉阻断且通气的大鼠中，向右侧第四胸段（T4）脊髓中间外侧核（IML）微量注射N - 甲基 - D - 天冬氨酸（NMDA，12皮摩尔）可立即增加同侧棕色脂肪组织（BAT）交感神经活动（SNA；峰值为对照值的 +492%）、呼出二氧化碳（+0.1%）、心率（+48次/分钟）和动脉血压（+8毫米汞柱）。当在T4 IML微量注射5 - 羟色胺（5 - HT，100皮摩尔）或5 - HT1A/5 - HT7受体激动剂8 - 羟基 - 二丙基氨基四氢萘（8 - OH - DPAT，600皮摩尔）之后立即进行T4 IML微量注射NMDA时，由NMDA引起的BAT SNA增加得到增强（曲线下面积：分别为仅注射NMDA反应的184%和259%）。相比之下，T4 IML微量注射5 - HT2受体激动剂DOI（28皮摩尔）并未增强NMDA引起的BAT SNA增加（为仅注射NMDA反应的101%）。向T4 IML微量注射选择性5 - HT1A拮抗剂WAY - 100635（500皮摩尔）加5 - HT7拮抗剂SB - 269970（500皮摩尔）可阻止5 - HT诱导的NMDA引起的BAT SNA增加的增强作用。当分别给药时，WAY - 100635（800皮摩尔）和SB - 269970（800皮摩尔）分别通过影响反应的幅度和持续时间来减弱8 - OH - DPAT诱导的NMDA引起的BAT SNA增加的增强作用。选择性5 - HT2受体拮抗剂酮色林（100皮摩尔）并未减弱由5 - HT或8 - OH - DPAT诱导的NMDA引起的BAT SNA增加的增强作用。这些结果表明，5 - HT1A/5 - HT7受体的激活可与IML内的NMDA受体激活协同作用，显著增加BAT SNA。
