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Am J Physiol Regul Integr Comp Physiol 294: R884-R894, 2008. First published December 19, 2007; doi:10.1152/ajpregu.00655.2007
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NEUROHUMORAL CONTROL OF CARDIOVASCULAR FUNCTION

Activation of 5-HT1A receptors in medullary raphé disrupts sleep and decreases shivering during cooling in the conscious piglet

J. W. Brown,1 E. A. Sirlin,1 A. M. Benoit,1 J. M. Hoffman,1 and R. A. Darnall1,2

Departments of 1Physiology and 2Pediatrics, Dartmouth Medical School, Lebanon, New Hampshire

Submitted 10 September 2007 ; accepted in final form 13 December 2007

Activation of 5-HT1A receptors in the medullary raphé 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 raphé 5-HT1A receptors. We previously showed in conscious piglets that activation of 5-HT1A receptors with (±)-8-hydroxy-2-(dipropylamino)-tetralin (8-OH-DPAT) in the paragigantocellularis lateralis (PGCL), a medullary region lateral to the raphé that contains substantial numbers of 5-HT neurons, eliminates rapid eye movement (REM) sleep and decreases shivering in a cold environment, but does not attenuate peripheral vasoconstriction. Hoffman JM, Brown JW, Sirlin EA, Benoit AM, Gill WH, Harris MB, Darnall RA. Am J Physiol Regul Integr Comp Physiol 293: R518–R527, 2007. We hypothesized that, during cooling, activation of 5-HT1A receptors in the medullary raphé 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 raphé resulted in alternating brief periods of non-REM 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 raphé. The effects of 8-OH-DPAT were prevented after dialysis of the selective 5-HT1A receptor antagonist WAY-100635. We conclude that, during cooling, exogenous activation of 5-HT1A receptors in the medullary raphé decreases both shivering and peripheral vasoconstriction. Our data are consistent with the hypothesis that neurons expressing 5-HT1A receptors in the medullary raphé facilitate spinal motor circuits involved in shivering, as well as sympathetic stimulation of other thermoregulatory effector mechanisms.

thermoregulation; serotonin; brain stem; raphé; the sudden infant death syndrome



Address for reprint requests and other correspondence: R. A. Darnall, Dept. of Physiology, Dartmouth Medical School, One Medical Center Dr., Borwell Bldg., Lebanon, NH 03756 (e-mail: robert.a.darnall{at}hitchcock.org)







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