Alteration by maternal pinealectomy of fetal and neonatal melatonin and dopamine D1 receptor binding in the suprachiasmatic nuclei.

The effects of maternal melatonin on fetal and neonatal melatonin and dopamine D1 receptor systems in the central nervous system, mainly in the suprachiasmatic nuclei (SCN), were investigated after pinealectomy of rats at day 7 of pregnancy. 125I-labelled iodomelatonin injected intravenously into the pregnant rats (at day 21) was transferred in considerable amount into the fetal circulation. In vitro autoradiography data demonstrated an increase in the melatonin binding activity in the fetal (embryonic day 21) and early postnatal SCN (postnatal day 3) caused by maternal pinealectomy. This upregulation of the melatonin receptor in the SCN was then normalized after the melatonin system of the neonate started to work. The pregnant rats themselves did not show such a change in their melatonin receptors in the SCN following pinealectomy. Dopamine D1 receptor binding was affected by pinealectomy exclusively in the SCN of fetal and neonatal rats as well as in that of mothers. These results clearly indicate that the fetal circadian clock in the SCN is controlled and prepared before birth to some extent by maternal melatonin rhythm.

Juvenile circadian core temperature rhythm in Wistar and lean (Fa/-) Zucker rat pups.

We compared the daily rhythms of cold defense in Wistar and lean (Fa/-) Zucker rat pups isolated from maternal care. Pups, born in a colony with lights-on from 7:00 to 19:00, were artificially reared from 10 to 13 days of age in continuous light at moderate cold loads, while we recorded core temperature (Tc) and metabolic rate (MR). Pups of both strains showed daily rhythms distinctly different from those of adult rats: on the first day of artificial rearing Tc steeply decreased shortly before the time of lights-on in the breeding colony and reached a daily minimum of 31.8 +/- 0.4 degree C at 7:17 +/- 17 min in Zucker pups (+/- SE, N = 24) and of 33.4 +/- 0.2 degree C at 8:59 +/- 9 min (N = 25) in Wistar pups. On each day, the average daily minimum Tc was significantly higher in Wistar than in Zucker rats, whereas the daily maximum Tc were close to 36 degrees C in both strains. The daily rhythms of MR resembled those of Tc. We conclude that circadian differences of cold defense, which must be expected to influence a variety of behavioral and physiological parameters, are not a peculiarity of Zucker rat pups but also occur, though with a smaller amplitude, in 10-day-old Wistar pups.

Pronounced juvenile circadian core temperature rhythms exist in several strains of rats but not in rabbits.

Torpor-like circadian variations of core temperature are well documented for suckling-age Zucker rat pups. To determine (1) whether this juvenile circadian rhythm is as strongly expressed in other rat strains, and (2) whether a similar rhythm is expressed in rabbit pups, we recorded core temperature and metabolic rate of artificially reared pups. Wistar, Brown Norway, and Long Evans pups were studied for 30 h under moderate cold loads (ambient temperature = 28 degrees C) when 9-11 days old, i.e. at the age and ambient temperature for which the rhythm has been most thoroughly characterized in Zucker rats. Chinchilla bastard rabbit pups were studied under similar conditions when they were 3-8 days old, the youngest age at which the rhythm can be easily detected in rats. Rat pups of each strain showed clear circadian rhythms with sharp decreases of core temperature and metabolic rate in subjective morning. Core temperature amplitudes were in the order Wistar < Brown Norway < Zucker < Long Evans strain. In contrast, the rabbit pups maintained stable high levels of core temperature and metabolic rate throughout the day. A torpor-like decrease of core temperature in the morning is thus not a peculiarity of the Zucker rat strain but also occurs in other pigmented rat strains, whereas rabbit pups at a similar developmental stage do not show a circadian core temperature rhythm.

Mapping of prostaglandin E2 binding sites in rat brain using quantitative autoradiography.

The density of specific prostaglandin E2 (PGE2) binding sites was quantitatively mapped in the rat brain using in vitro autoradiography. The anterior wall of the third ventricle and the nucleus solitary tract were found to have a very high density of binding sites (greater than 15 fmol/mg tissue). Two thalamic nuclei (paraventricular and anteroventral nuclei) and the dorsal parabrachial nucleus contained a high density of binding sites (10-15 fmol/mg tissue). Entorhinal cortex, ventral hippocampus, amygdala, dorsomedial hypothalamus, mammillary complex, some thalamic nuclei, central gray, superior colliculus, raphe nuclei, locus coeruleus, spinal trigeminal nucleus (caudal part) and the dorsal horn of the spinal cord (laminae 1 and 2) had each a moderate density of binding sites (5-10 fmol/mg tissue). Binding tended to occur in brain regions rich in neuronal cell bodies or neuronal cell processes (dendrites and axon terminals). PGE1, whose central actions are very similar to those of PGE2, had essentially the same pattern of binding sites as did PGE2 throughout the entire brain, suggesting there are receptors common to these two PGEs. In addition to already known functions of receptors common to these two PGEs. In addition to already known functions of PGE2 in the hypothalamus, which include fever genesis, promotion of wakefulness, cardiovascular control and LH-RH release, the unique distribution of extrahypothalamic PGE2 binding sites found in this study suggests its involvement in the processing or modulation of viscerosensory, somatosensory (nociceptive and possibly thermal) and visual inputs as well as in the central integration of autonomic and limbic functions.(ABSTRACT TRUNCATED AT 250 WORDS)

Maternal thermal stimulation changes metabolic activity in fetal hypothalamus.

To study whether the central nervous system in the perinatal fetal rat can operate during maternal cooling and warming, we examined the 2-deoxy-D-[14C]glucose ([14C]DG) uptake in the fetal brain. Full-term pregnant rats were placed at three different ambient temperatures of 35-37 degrees C, 24-25 degrees C and 0-10 degrees C. Saline containing 20 microCi/100 g of [14C]DG was injected into the superior caval vein in the pregnant rats. Forty-five min after the injection, the mother rats were decapitated and the fetal brains were taken out for autoradiography. The [14C]DG uptake was significantly influenced by maternal thermal stimulation in the hypothalamus and not in other brain regions examined such as the cerebral cortex, the basal ganglia and the limbic nuclei. Glucose utilization in the fetal anterior hypothalamus, paraventricular hypothalamus and dorsomedial hypothalamus significantly increased when the mother rat was exposed to heat compared to when the mother rat was in the thermoneutral condition. During maternal cooling, glucose utilization in the ventromedial hypothalamus and dorsomedial hypothalamus significantly decreased. There was no area activated by cooling and/or inhibited by warming. Compared to a similar study in adult rats (Am. J. Physiol., 248 (1985) R84-92), the present results suggest that although the perinatal fetal brain does not respond to thermal stimulation in terms of glucose utilization as fully as the adults, a few hypothalamic nuclei have already acquired thermal responses, which might be a possible neuronal basis for the thermoregulatory responses just after birth in rats.

Metabolic activation of the fetal rat brain.

In the present study, we tried to examine whether the 2-deoxy-D-[14C]glucose (2-DG) technique is useful to investigate the metabolic activity of fetal rat brain in the maternal uterus. The result shows that metabolic mapping of the fetal brain was clearly obtained by means of the 2-DG technique.

Thermal responses of ventromedial hypothalamic neurons in vivo and in vitro.

The ventromedial hypothalamic neurons were recorded in anesthetized rats and in slice preparations. Whereas almost all thermosensitive neurons (27 out of 28) in the slice preparations showed warm sensitivity, cold-responsive neurons were recorded more frequently than warm-responsive ones during preoptic thermal stimulation in anesthetized rats. These results suggest that most cold-responsive neurons excited by preoptic cooling in the anesthetized rats were influenced by synaptic inputs.

The central efferent mechanism of brown adipose tissue thermogenesis induced by preoptic cooling.

This study was performed to investigate central efferent mechanisms for brown adipose tissue thermogenesis. In unanesthetized rats, the effects of local anesthesia of the ventromedial hypothalamus, anterior hypothalamus, and lateral hypothalamus were observed on the brown adipose tissue thermogenesis induced by preoptic cooling. Rats had a thermode, thermocouple, and bilateral injection cannulae chronically implanted in the hypothalamus and a thermocouple beneath the interscapular brown adipose tissue. The experiments were done at an ambient temperature of 24-25 degrees C. Preoptic cooling increased brown adipose tissue and colonic temperatures without shivering. Injecting lidocaine bilaterally into the ventromedial hypothalamus during preoptic cooling reduced brown adipose tissue temperature (Tbat). The mean maximum decrease of Tbat was 0.51 +/- 0.26 degrees C and occurred 5-8 min after lidocaine injection. When lidocaine was injected into the anterior hypothalamus, Tbat increased. The mean maximum increase of Tbat was 0.85 +/- 0.29 degrees C and occurred 4-9 min after lidocaine injection. In the lateral hypothalamus, lidocaine had no effect on Tbat. Tbat was not influenced by injection of saline into the ventromedial, anterior, or lateral hypothalamus. The efferent pathway from preoptic to brown adipose tissue may thus traverse the medial part of hypothalamus. The ventromedial hypothalamus facilitates and anterior hypothalamus inhibits brown adipose tissue thermogenesis induced by preoptic cooling.

Response of glucose-responsive ventromedial hypothalamic neurons to scrotal and preoptic thermal stimulation in rats.

Almost all ventromedial hypothalamic (VMH) neurons facilitated by electro-osmotic application of glucose responded to scrotal thermal stimulation. On the other hand, only 50% of neurons which did not respond to glucose responded to the thermal stimulation. The VMH neurons facilitated or inhibited by scrotal warming were mostly facilitated or inhibited by preoptic warming, respectively. These results suggest that thermal signals from scrotal skin and preoptic area were conveyed to VMH neurons, especially to glucose-responsive ones, and could influence feeding control.

Involvement of ventromedial hypothalamus in brown adipose tissue thermogenesis induced by preoptic cooling in rats.

In unanesthetized rats, preoptic (PO) cooling increased brown adipose tissue (BAT) temperature (Tbat). Tbat was kept at a higher level by PO cooling, but lidocaine injected into the ventromedial hypothalamus (VMH) decreased Tbat and saline had no effect. These results indicate VMH is involved in BAT thermogenesis induced by PO cooling.