Inhibition of Serotonergic Neurons in the Nucleus Paragigantocellularis Lateralis Fragments Sleep and Decreases Rapid Eye Movement Sleep in the Piglet: Implications for Sudden Infant Death Syndrome

Darnall, Robert A.; Harris, Michael B.; Gill, Waltus H.; Hoffman, Jill M.; Brown, Justin W.; Niblock, Mary M.

doi:10.1523/jneurosci.1770-05.2005

Cited by 41 publications

(62 citation statements)

References 79 publications

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“…ethyl}-N-2-pyridinylcyclohexane-carboxamide (WAY-100635) and attenuated after destroying PGCL 5-HT neurons with 5,7-dihydroxytryptamine, indicating that they were largely the result of activating 5-HT 1A autoreceptors located on 5-HT neurons (17). In other experiments in conscious piglets focused on the cardiorespiratory function of the medullary raphé, microdialysis of 8-OH-DPAT produced an increase in WAKE and decreased sleep (50).…”

Section: Methoxyphenyl)-1-piperazinyl]-mentioning

confidence: 99%

“…Almost 75% of SIDS infants studied have decreased binding to 5-HT 1A receptors and increased numbers of 5-HT neurons in all of the medullary serotonergic nuclei, including the medullary raphé and PGCL (41-43, 65, 69), groups of neurons homologous to those that have been found to be important in thermoregulation and sleep in animals (12,17,53). We hypothesize that dysfunction in these regions may increase the risk for SIDS by altering sleep architecture and protective reflexes to stressors encountered during sleep, including thermal challenges.…”

Section: Methoxyphenyl)-1-piperazinyl]-mentioning

confidence: 99%

“…A major goal was to determine whether activation of 5-HT 1A receptors in the medullary raphé of conscious piglets during continuous cooling would attenuate both shivering and peripheral vasoconstriction. In addition, we wanted to determine whether activation of 5-HT 1A receptors would eliminate REM, as our laboratory has observed during 8-OH-DPAT dialysis in the PGCL (17).…”

Section: Methoxyphenyl)-1-piperazinyl]-mentioning

confidence: 99%

“…Moreover, piglets do not have BAT and use shivering as the primary mechanism for thermoregulatory heat production and thus are excellent models in which to study shivering. In recent experiments in conscious piglets, we showed that activation of 5-HT 1A receptors in the juxtafacial paragigantocellularis lateralis (PGCL), a region lateral to the raphé within the rostrocaudal dimension of the facial nucleus containing substantial numbers of 5-HT neurons (17,61), significantly reduced shivering during cooling, but had little or no effect on peripheral vasoconstriction (34). A role for medullary raphé neurons in modulating shivering is also suggested by recent evidence that the activity of fusimotor fibers innervating skeletal muscle during skin cooling can be attenuated by the microinjection of glycine into the medullary raphé (87).…”

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“…Our laboratory showed previously that dialysis of 8-OH-DPAT into the PGCL, both at thermoneutrality and during continuous cooling, results in fragmented sleep with alternating brief periods of non-rapid eye movement (NREM) sleep and WAKE, and an almost complete elimination of rapid eye movement (REM) sleep (17,34). These effects were eliminated after blocking the 5-HT 1A receptor with the selective 5-HT 1A antagonist N-{2- [4-(2-…”

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Activation of 5-HT_1Areceptors in medullary raphé disrupts sleep and decreases shivering during cooling in the conscious piglet

Brown¹,

Sirlin²,

Benoit³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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Activation of 5-HT 1A 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-HT 1A receptors. We previously showed in conscious piglets that activation of 5-HT 1A receptors with (Ϯ)-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-HT 1A receptors in the medullary raphé would also eliminate REM sleep and, in contrast to activation of 5-HT 1A 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-HT 1A receptor antagonist WAY-100635. We conclude that, during cooling, exogenous activation of 5-HT 1A receptors in the medullary raphé decreases both shivering and peripheral vasoconstriction. Our data are consistent with the hypothesis that neurons expressing 5-HT 1A 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 MANY NEURONS IN THE MEDULLARY raphé, including serotonergic (5-HT) neurons, project to the intermediolateral cell column (IML) of the spinal cord and modulate sympathetic outflow to thermoregulatory effector mechanisms, including brown adipose tissue (BAT) thermogenesis, vasoconstriction of thermoregulatory cutaneous vascular beds, and heart rate (HR) (14,53,58,86,89). Studies in anesthetized and conscious animals have shown that activation of 5-HT 1A receptors in the medullary raphé with the selective agonist, (Ϯ)-8-hydroxy-2-(dipropylamino)-tetralin (8-OH-DPAT), attenuates sympathetic outflow to BAT and peripheral vessels when previously elevated by LPS, leptin, or cooling (11,52,59,63,64).There is mounting evidence that medullary raphé 5-HT neurons modulate sympathetically mediated thermoregulatory mechanisms; however, little is known about the role of medullary raphé 5-HT neurons in shivering thermogenesis. Shivering is an involuntary tremor that i...

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Section: Methoxyphenyl)-1-piperazinyl]-mentioning

confidence: 99%

Section: Methoxyphenyl)-1-piperazinyl]-mentioning

confidence: 99%

Section: Methoxyphenyl)-1-piperazinyl]-mentioning

confidence: 99%

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