Hoffman J M, Brown J W, Sirlin E A, Benoit A M, Gill W H, Harris M B, Darnall R A
Department of Physiology, Dartmouth Medical School, One Medical Center Drive, Lebanon, NH, USA.
Am J Physiol Regul Integr Comp Physiol. 2007 Jul;293(1):R518-27. doi: 10.1152/ajpregu.00816.2006. Epub 2007 Apr 4.
Activation of 5-HT(1A) receptors in the medullary raphé decreases sympathetic outflow to thermoregulatory mechanisms, including brown adipose tissue (BAT), thermogenesis, and peripheral vasoconstriction when these mechanisms are previously activated with leptin, prostaglandins, or cooling. These same mechanisms are also inhibited during rapid eye movement (REM) sleep. It is not known whether shivering is also modulated by medullary raphé neurons. We previously showed in the conscious piglet that activation of 5-HT(1A) receptors with 8-OH-DPAT (DPAT) in the paragigantocellularis lateralis (PGCL), a medullary region lateral to the midline raphé that contains 5-HT neurons, decreases heart rate, body temperature and muscle activity during non-rapid eye movement (NREM) sleep. We therefore hypothesized that activation of 5-HT(1A) receptors in the PGCL would also attenuate shivering and peripheral vasoconstriction during cooling. During REM sleep in a cool environment, shivering, carbon dioxide production, and body temperature decreased, and ear capillary blood flow and ear skin temperature increased. Shivering associated with rapid cooling was attenuated after dialysis of DPAT into the PGCL. In animals maintained in a continuously cool environment, dialysis of DPAT into the PGCL attenuated shivering and decreased body temperature, but there were no significant increases in ear capillary blood flow or ear skin temperature. We conclude that both naturally occurring REM sleep and exogenous activation of 5-HT(1A) receptors in the PGCL are associated with a suspension of shivering during cooling. Our data are consistent with the hypothesis that 5-HT neurons in the PGCL facilitate oscillating spinal motor circuits involved in shivering but are less involved in modulating sympathetically mediated thermoregulatory mechanisms.
当瘦素、前列腺素或降温预先激活延髓中缝5-羟色胺（5-HT）(1A) 受体时，其激活会减少对体温调节机制的交感神经输出，这些机制包括棕色脂肪组织（BAT）、产热和外周血管收缩。在快速眼动（REM）睡眠期间，这些相同的机制也会受到抑制。目前尚不清楚寒颤是否也受延髓中缝神经元的调节。我们之前在清醒的仔猪身上发现，在外侧巨细胞旁核（PGCL）（中缝中线外侧的一个延髓区域，含有5-HT神经元）中用8-羟基二丙胺基四氢萘（8-OH-DPAT，DPAT）激活5-HT(1A) 受体，会降低非快速眼动（NREM）睡眠期间的心率、体温和肌肉活动。因此，我们推测在PGCL中激活5-HT(1A) 受体也会减弱降温期间的寒颤和外周血管收缩。在凉爽环境中的REM睡眠期间，寒颤、二氧化碳产生量和体温下降，耳毛细血管血流量和耳皮肤温度升高。向PGCL中透析DPAT后，与快速降温相关的寒颤减弱。在持续处于凉爽环境的动物中，向PGCL中透析DPAT会减弱寒颤并降低体温，但耳毛细血管血流量或耳皮肤温度没有显著升高。我们得出结论，自然发生的REM睡眠和PGCL中5-HT(1A) 受体的外源性激活都与降温期间寒颤的暂停有关。我们的数据与以下假设一致，即PGCL中的5-HT神经元促进参与寒颤的脊髓运动回路振荡，但较少参与调节交感神经介导的体温调节机制。
