Submitted on September 10, 2007
Accepted on December 13, 2007
Activation of 5-HT1A receptors in medullary raphe disrupts sleep and decreases shivering during cooling in the conscious piglet
Justin W. Brown1, Edward A. Sirlin2, Andrea M. Benoit3, Jill M. Hoffman4, and Robert A Darnall5*
1 Biology, James Madison University, Harrisonburg, Virginia, United States
2 Medicine, Penn State College of Medicine, Hershey, Pennsylvania, United States
3 Medicine, University of New England College of Osteopathic Medicine, Biddeford, Maine, United States
4 Neuroscience, University of Vermont, Burlington, Vermont, United States
5 Department of Physiology, Dartmouth Medical School, Lebanon, New Hampshire, United States
* To whom correspondence should be addressed. E-mail: robert.a.darnall{at}hitchcock.org.
Activation of 5-HT1A receptors in the medullary raphe decreases sympathetically mediated brown adipose tissue (BAT) thermogenesis and peripheral vasoconstriction when previously activated with leptin, LPS, prostaglandins, or cooling. It is not known whether shivering is also modulated by medullary raphe 5-HT1A receptors. We previously showed in conscious piglets that activation of 5-HT1A receptors with 8-OH-DPAT in the paragigantocellularis lateralis (PGCL), a medullary region lateral to the raphe that contains substantial numbers of 5-HT neurons, eliminates REM sleep and decreases shivering in a cold environment, but does not attenuate peripheral vasoconstriction. We hypothesized that during cooling, activation of 5-HT1A receptors in the medullary raphe would also eliminate REM sleep and, in contrast to activation of 5-HT1A receptors in the PGCL, would attenuate both shivering and peripheral vasoconstriction. In a continuously cool environment, dialysis of 8-OH-DPAT into the medullary raphe resulted in alternating brief periods of NREM sleep and wakefulness and eliminated REM sleep as observed when 8-OH-DPAT is dialyzed into the PGCL. Moreover, both shivering and peripheral vasoconstriction were significantly attenuated after 8-OH-DPAT dialysis into the medullary raphe. The effects of 8-OH-DPAT were prevented after dialysis of the selective 5-HT1A receptor antagonist, WAY 100635. We conclude that during cooling, activation of 5-HT1A receptors in the medullary raphe decreases both shivering and peripheral vasoconstriction. Our data are consistent with the hypothesis that neurons expressing 5-HT1A receptors in the medullary raphe facilitate spinal motor circuits involved in shivering as well as sympathetic stimulation of other thermoregulatory effector mechanisms.
