Activation of 5-HT_1Areceptors in the paragigantocellularis lateralis decreases shivering during cooling in the conscious piglet

Abstract

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.

Activation of 5-HT1Areceptors in medullary raphé disrupts sleep and decreases shivering during cooling in the conscious piglet

“…Our laboratory's surgical procedures have been described in detail previously (15)(16)(17)34). Briefly, under sterile conditions and using isofluorane anesthesia, a dual-lumen catheter was placed into the femoral artery and advanced into the abdominal aorta, and a telemetric thermistor was placed into the peritoneal cavity.…”

“…Throughout the experiment, piglet behavior was also video recorded and digitized for later sleep scoring. Shivering was assessed by measuring the percent time shivering, the number of shivering bouts/minute, and changes in integrated neck EMG (nEMG) activity, as we have previously described (34).…”

“…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).…”

“…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-…”

Defects in Breathing and Thermoregulation in Mice with Near-Complete Absence of Central Serotonin Neurons

“…Some 5-HT neurons project to the intermediolateral cell column (Cano et al, 2003), and increase their activity in response to both environmental (Martin-Cora et al, 2000) and hypothalamic (Nason and Mason, 2006) cooling. Additionally, systemic or raphé/parapyramidal application of the 5-HT 1A receptor agonist 8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT) decreases core temperature and impairs shivering (Hoffman et al, 2007), inhibits cold-induced vasoconstriction (Ootsuka and Blessing, 2003), and attenuates leptin-evoked activation of brown adipose tissue (BAT) sympathetic outflow (Morrison, 2004a). However, it remains unclear if 5-HT neurons are presympathetic motor neurons that drive thermogenesis and peripheral vasoconstriction, or if they simply modulate descending drive (Nason and Mason, 2006).…”