Ootsuka Y, Heidbreder C A, Hagan J J, Blessing W W
Department of Human Physiology, Centre for Neuroscience, Flinders University, Bedford Park, South Australia 5042, Australia.
Neuroscience. 2007 Jun 15;147(1):127-35. doi: 10.1016/j.neuroscience.2007.04.015. Epub 2007 May 21.
Dopamine D(2)-like receptor agonists cause hypothermia. We investigated whether inhibiting heat production by interscapular brown adipose tissue (iBAT), a major thermogenic organ in rats, contributes to hypothermia caused by dopamine D(2)-like receptor agonists. Temperature of iBAT and tail artery blood flow were measured in conscious rats. Activity in postganglionic sympathetic nerves supplying iBAT was assessed in anesthetized rats. Conscious rats were housed in a warm cage maintained at 26-28 degrees C and then transferred to a cold cage at 5-10 degrees C to induce iBAT thermogenesis. Cold exposure increased iBAT temperature (+0.7+/-0.1 degrees C, 30 min after transferring to the cold cage, P<0.01, n=54). The mixed dopamine D(2)/D(3) receptor agonist, 7-hydroxy-2-(di-n-propylamino)tetralin (7-OH-DPAT, 0.5 mg/kg s.c.) reversed the cold-induced increase in iBAT temperature (-2.8+/-0.2 degrees C at 30 min after 7-OH-DPAT treatment during cold exposure vs. +0.3+/-0.1 degrees C at 30 min after vehicle treatment during cold exposure, n=8). These temperature changes were blocked by pre-treatment with the D(2) receptor antagonists spiperone (20 microg/kg i.p.) and L-741,626 (2.5 mg/kg i.p.), but not by the selective D(3) receptor antagonist SB-277011A (10 mg/kg i.p.). Another mixed dopamine D(2)/D(3) receptor agonist, quinpirole (0.5 mg/kg s.c.) also reversed cold-induced iBAT thermogenesis, and this effect was also prevented by pre-treatment with spiperone, but not with a peripherally acting dopamine receptor antagonist, domperidone (2 mg/kg s.c.). Neither 7-OH-DPAT nor quinpirole reversed cutaneous vasoconstriction elicited by cold exposure. In anesthetized rats, quinpirole (0.5 mg/kg i.v.) abolished iBAT sympathetic nerve discharge elicited by cooling the trunk, and this change was reversed by spiperone (20 microg/kg i.v.). These results demonstrate that activation of CNS dopamine D(2) receptors inhibits sympathetically-mediated iBAT thermogenesis in response to cold exposure. Furthermore, they suggest that in rats hypothermia induced by dopamine D(2) receptor agonists in cold environments is mainly due to decreased heat production rather than to increased heat loss.
多巴胺D(2)样受体激动剂可导致体温过低。我们研究了抑制大鼠主要产热器官肩胛间棕色脂肪组织（iBAT）的产热是否会导致多巴胺D(2)样受体激动剂引起的体温过低。在清醒大鼠中测量iBAT的温度和尾动脉血流量。在麻醉大鼠中评估供应iBAT的节后交感神经的活性。将清醒大鼠饲养在维持在26-28摄氏度的温暖笼子中，然后转移到5-10摄氏度的寒冷笼子中以诱导iBAT产热。冷暴露使iBAT温度升高（转移到寒冷笼子30分钟后升高0.7±0.1摄氏度，P<0.01，n=54）。混合多巴胺D(2)/D(3)受体激动剂7-羟基-2-(二正丙基氨基)四氢萘（7-OH-DPAT，0.5mg/kg皮下注射）逆转了冷诱导的iBAT温度升高（冷暴露期间7-OH-DPAT治疗后30分钟时为-2.8±0.2摄氏度，而冷暴露期间给予溶剂治疗后30分钟时为+0.3±0.1摄氏度，n=8）。这些温度变化被D(2)受体拮抗剂螺哌隆（20μg/kg腹腔注射）和L-741,626（2.5mg/kg腹腔注射）预处理所阻断，但未被选择性D(3)受体拮抗剂SB-277011A（10mg/kg腹腔注射）阻断。另一种混合多巴胺D(2)/D(3)受体激动剂喹吡罗（0.5mg/kg皮下注射）也逆转了冷诱导的iBAT产热，并且这种作用也被螺哌隆预处理所阻止，但未被外周作用的多巴胺受体拮抗剂多潘立酮（2mg/kg皮下注射）阻止。7-OH-DPAT和喹吡罗均未逆转冷暴露引起的皮肤血管收缩。在麻醉大鼠中，喹吡罗（0.5mg/kg静脉注射）消除了冷却躯干引起的iBAT交感神经放电，并且这种变化被螺哌隆（20μg/kg静脉注射）逆转。这些结果表明，中枢神经系统多巴胺D(2)受体的激活抑制了冷暴露引起的交感神经介导的iBAT产热。此外，它们表明在寒冷环境中多巴胺D(2)受体激动剂诱导的大鼠体温过低主要是由于产热减少而非散热增加。
