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.

Serotonergic receptor binding is altered in the medullary serotonergic nuclei, including the paragigantocellularis lateralis (PGCL), in many infants who die of sudden infant death syndrome (SIDS). The PGCL receives inputs from many sites in the caudal brainstem and projects to the spinal cord and to more rostral areas important for arousal and vigilance. We have shown previously that local unilateral nonspecific neuronal inhibition in this region with GABA(A) agonists disrupts sleep architecture. We hypothesized that specifically inhibiting serotonergic activity in the PGCL would result in less sleep and heightened vigilance. We analyzed sleep before and after unilaterally dialyzing the 5-HT1A agonist (+/-)-8-hydroxy-2-(dipropylamino)-tetralin (8-OH-DPAT) into the juxtafacial PGCL in conscious newborn piglets. 8-OH-DPAT dialysis resulted in fragmented sleep with an increase in the number and a decrease in the duration of bouts of nonrapid eye movement (NREM) sleep and a marked decrease in amount of rapid eye movement (REM) sleep. After 8-OH-DPAT dialysis, there were decreases in body movements, including shivering, during NREM sleep; body temperature and heart rate also decreased. The effects of 8-OH-DPAT were blocked by local pretreatment with N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexane-carboxamide, a selective 5-HT1A antagonist. Destruction of serotonergic neurons with 5,7-DHT resulted in fragmented sleep and eliminated the effects of subsequent 8-OH-DPAT dialysis on REM but not the effects on body temperature or heart rate. We conclude that neurons expressing 5-HT1A autoreceptors in the juxtafacial PGCL are involved in regulating or modulating sleep. Abnormalities in the function of these neurons may alter sleep homeostasis and contribute to the etiology of SIDS.

The Pre-Optic Anterior Hypothalamus (POAH) partially mediates the hypothermic response to hemorrhage in rats.

Two sets of experiments were performed to characterize the role of the Pre-Optic Area of the Anterior Hypothalamus (POAH) in the decrease in set point and hypothermia that follows severe hemorrhage. In the first set, lidocaine or artificial cerebrospinal fluid (ACSF) was microinjected into the POAH of rats at the time of hemorrhage. Lidocaine microinjection attenuated the hemorrhagic hypothermia by approximately 50%. The mean drop in core temperature (Tc) following hemorrhage was 1.5 degrees C with ACSF microinjection (N = 6), 0.70 degrees C (N = 6) with lidocaine, and 1.77 degrees C (N = 6) after sham microinjection. This partial attenuation of the hemorrhagic hypothermic response indicates that an intact POAH is necessary for at least some of the hypothermia following hemorrhage. In the second experimental set, hypothalamic tissue temperature (Thyp) was modulated in an attempt to alter the hemorrhagic hypothermic response. Bilateral closed-ended cannulas were inserted into the POAH. One cannula consisted of a water-perfused thermode to change local tissue temperature. The other housed a thermocouple to measure local temperature. The effectiveness of the thermode was first confirmed in conscious rats, evidenced by an inverse deflection in Tc upon Thyp modulation. Then, the POAH region was either heated, cooled, or sham perfused following hemorrhage. The mean drop in Tc following hemorrhage was 2.16 degrees C (N = 5) with hypothalamic heating, 1.35 degrees C (N = 5) with cooling, and 1.44 degrees C (N = 5) following the sham perfusion control. Heating of the POAH significantly exacerbated the hemorrhagic hypothermic response. These data further suggest that the POAH is at least partially responsible for mediating hemorrhagic hypothermia.

Thermoregulatory set point decreases after hemorrhage in rats.

Hemorrhage in rats causes a drop in body core temperature that is proportional to the hemorrhage volume. We tested the hypothesis that the hemorrhagic hypothermia is due to a downward shift in the thermoregulatory set point. If so, rats subjected to hemorrhage would prefer a cooler ambient temperature to enhance heat loss during the posthemorrhage period. Male Sprague-Dawley rats were fitted with carotid arterial catheters and biotelemetry temperature probes. Two days later, rats were placed in a temperature gradient chamber that allowed the rat to move between ambient temperatures of 15 degrees C to 40 degrees C. Rat location within the gradient was recorded as the selected ambient temperature. After 48 h, a 24 mL/kg hemorrhage was induced via the carotid cannula followed by a 24-h recovery period in the gradient. Body core and selected ambient temperatures significantly decreased after hemorrhage. Within 50 min, selected ambient temperature decreased by 11 degrees C, and returned to normal 100 min after hemorrhage. Within 80 min after hemorrhage, core temperature decreased by 2.3 degrees C, and returned to normal by 8 h after hemorrhage. Expanded analysis of the first hour after hemorrhage showed that reduction in selected ambient temperature preceded the drop in body core temperature. Importantly, the decrease in selected ambient temperature persisted even during the peak decrease in body core temperature. These results indicate that a decrease in thermoregulatory set point contributes to the drop in body core temperature after hemorrhage.