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Biomedical subjects

T L Stanton

Publications and source records attributed to T L Stanton.

At least 19 recordsLinked to original sources

Major changes in the brain histamine system of the ground squirrel Citellus lateralis during hibernation.

Hibernation in mammals such as the rodent hibernator Citellus lateralis is a physiological state in which CNS activity is endogenously maintained at a very low, but functionally responsive, level. The neurotransmitter histamine is involved in the regulation of diurnal rhythms and body temperature in nonhibernators and, therefore, could likely play an important role in maintaining the hibernating state. In this study, we show that histamine neuronal systems undergo major changes during hibernation that are consistent with such a role. Immunohistochemical mapping of histaminergic fibers in the brains of hibernating and nonhibernating golden-mantled ground squirrels (C. lateralis) showed a clear increase in fiber density during the hibernating state. The tissue levels of histamine and its first metabolite tele-methylhistamine were also elevated throughout the brain of hibernating animals, suggesting an increase in histamine turnover during hibernation, which occurs without an increase in histidine decarboxylase mRNA expression. This hibernation-related apparent augmentation of histaminergic neurotransmission was particularly evident in the hypothalamus and hippocampus, areas of importance to the control of the hibernating state, in which tele-methylhistamine levels were increased more than threefold. These changes in the histamine neuronal system differ from those reported for the metabolic pattern in other monoaminergic systems during hibernation, which generally indicate a decrease in turnover. Our results suggest that the influence of histamine neuronal systems may be important in controlling CNS activity during hibernation.

Animals↗

Changes in striatal dopamine metabolism during the development of morphine physical dependence in rats: observations using in vivo microdialysis.

The present study examined the effect of prolonged morphine treatment on striatal dopamine (DA) release and metabolism, during the initial phase of the development of morphine dependence. Sprague-Dawley rats were implanted with chronic guides for microdialysis of the striatum. Morphine (two 75-mg pellets, subcutaneous implant) or placebo was given (12 hr) to pentobarbital anesthetized animals. Following recovery from anesthesia, morphine physical dependence was verified by the naloxone-evoked abstinence syndrome. Morphine produced significant increases in the dialysate level of DA nad its metabolites (DOPAC and HVA) above baseline compared to placebo treatment. HVA levels began to increase immediately following morphine administration, whereas DA and DOPAC levels began to increase after a latency of one and three hr, respectively. Morphine effects on striatal DA metabolism included changes in the metabolic disposition of DA. Increases in HVA concentration accompanied increases in DOPAC concentration up to a threshold value of DOPAC efflux; further increases in DOPAC level were associated with decreases in HVA level. These in vivo data suggest that morphine-induced changes in the regulation of striatal dopaminergic function may be an important component of the development of physical dependence.

3,4-Dihydroxyphenylacetic Acid↗

Reduction of hibernation bout duration by intraventricular infusion of met-enkephalin.

The potential of brain met-enkephalin (met-enk) systems to modulate central nervous system (CNS) activity during periods of general depression (modeled by the mammalian hibernation state) was studied in the ground squirrel (Citellus lateralis). Following entrance into hibernation, continuous met-enk infusion into the lateral ventricle (1 microliter/h; 0.2, 1 and 5 micrograms/microliter) produced a dose-dependent reduction in bout duration ranging from 1.2 to 3.9 days (13.8-44.6% of baseline bout duration). We suggest that the activity of met-enk-releasing neurons may serve to increase the excitability of the depressed CNS, thus accelerating the termination of the hibernation bout.

Animals↗

Thyrotropin-releasing hormone action in the preoptic/anterior hypothalamus decreases thermoregulatory set point in ground squirrels.

Earlier work has shown that thyrotropin releasing hormone (TRH) produces dose-dependent decreases in body temperature (Tb) and metabolic rate when microinjected into the dorsal hippocampus (HPC) or preoptic/anterior hypothalamus (PO/AH) of awake ground squirrels. This study employed a behavioral paradigm to investigate the possibility that TRH-induced hypothermia is associated with a decrease in thermoregulatory set point. Six animals were successfully trained to press a bar for radiant heat escape and cool air reinforcement in order to obtain a cooler ambient temperature (Ta). During experimental testing, the animals were microinjected remotely with TRH (10-1000 ng/microliters) or a control solution (sterile saline or TRH-OH) into the PO/AH. The micro-injections were delivered via bilateral injection cannulae inserted through chronic bilateral cannula guides that had been stereotaxically implanted under pentobarbital anesthesia. Cumulative and time-integrated bar presses were obtained on a computer generated display. Tb, measured in the brain via a bead-type thermistor, and chamber Ta were recorded continuously. Following TRH administration, a significant increase in mean bar-press rate was observed during the period in which Tb was falling, when compared to a comparable time period just prior to the microinjection. These findings complement results obtained from four animals that were trained to press a bar for heat reinforcement in a cold (- 10 degrees C) environment. In this alternative behavioral paradigm, microinjection of TRH into the PO/AH or HPC induced a decrease in mean bar-press rate as Tb was falling. The results support the hypothesis that TRH-induced hypothermia in golden-mantled ground squirrels is achieved by lowering thermoregulatory set point.

Animals↗

Seasonal and state-dependent changes in brain TRH receptors in hibernating ground squirrels.

Quantitative autoradiography was used to localize and quantify thyrotropin-releasing hormone (TRH) receptors in the brain of hibernating (H), winter euthermic (WE), and summer euthermic (SE) animals to further explore the state-dependent physiological and behavioral effects of TRH in ground squirrels. The pattern of [3H]MeTRH binding (Kd 6.7 +/- 0.1 nM) was heterogeneous and highly concentrated in structures primarily associated with the limbic forebrain. Statistically significant seasonal changes (SE vs. WE) were reflected by decreases in TRH receptor binding in the arcuate nucleus, dorsomedial nucleus, and ventral pallidum of WE animals. Increased binding in WE animals was evident in the suprachiasmatic nucleus and choroid plexus of the lateral ventricles. Significant state-dependent changes (WE vs. H) were characterized by decreases in TRH receptor binding in the hypothalamic paraventricular nucleus, medial preoptic area, ventral tegmental area, and choroid plexus of the lateral ventricles of H animals. Increased binding occurred in the anterior cortical nucleus of the amygdala in H animals. The results suggest that naturally occurring changes in central TRH systems may be important in the mediation of physiological and behavioral processes that undergo seasonal and state-dependent adjustments in hibernating mammals.

Animals↗

Estimating milk, fat, and protein lactation curves with a test day model.

Test day models were used to estimate lactation curves for milk, fat, protein, fat percentage, and protein percentage and to study the influence of age, season, and herd productivity on Holstein lactation curves. Random effects of lactation within herd and fixed effects of herd test date were absorbed. Fixed effects of cow's age on test day and either DIM (57 divisions) by parity (1, 2, greater than or equal to 3) class or season of calving (winter or summer) by DIM by parity class were estimated. Lactation curves for yield traits derived from DIM solutions were flatter for first versus later lactation, even without addition of age effects. Differences between lactation curves for the two seasons were slight, suggesting that most observed seasonal differences are caused by seasonal productivity accounted for by herd test date effects. At peak, winter calving cows yielded slightly more milk of similar fat percentage but of lower protein percentage than those calving in summer. Data were also partitioned into nine subsets based on rolling herd milk and fat percentage. Lactation curves for yield traits, but not percentage traits, varied with rolling herd milk. Lactation curves for fat yield and percentage varied with rolling herd fat percentage.

Age Factors↗

The area of 2-[125I] iodomelatonin binding in the pars tuberalis of the ground squirrel is decreased during hibernation.

Quantitative receptor autoradiography was used to analyze 2-[125I]iodomelatonin binding sites in the brains of golden-mantled ground squirrels (Citellus lateralis). Specific binding appeared to be discretely localized to the pars tuberalis region of the pituitary that surrounds the medial basal hypothalamus. The total area of binding was significantly decreased in brains of hibernating squirrels as compared to those of awake, euthermic animals. These findings support a role for melatonin receptors of the pars tuberalis in seasonal behavior.

Animals↗

Genotype by environment interaction for Holstein milk yield in Colombia, Mexico, and Puerto Rico.

Components of (co)variance and genetic parameters were estimated by REML procedures from first lactation mature equivalent Holstein milk records from 54,604 Colombian, Mexican, and Puerto Rican cows and 198,079 US cows. The objective was to determine the cause of heterogeneous daughter response to sire selection for milk yield between the regions. Data from Latin America were partitioned by country and by herd-year SD class for milk to obtain five joint analyses between the US and Latin America, low herd-year SD, high herd-year SD, Colombia, and Mexico. Sire and residual variances for milk were 41 and 29% smaller in Latin America than in the US, 47 and 58% smaller for low than for high herd-year SD, and 31 and 49% smaller for Colombia than for Mexico. Resultant heritabilities ranged from .20 to .29. Genetic correlations for milk yield between the US and Latin America, low and high herd-year SD, Colombia, and Mexico were .91, .82, .89, .78, and .90. Expected correlated responses for milk in Latin America, low and high herd-year SD, Colombia, and Mexico were 70, 53, 79, 56, and 78% of the direct response in the US. The scaling effects of heterogeneous variance resulted in smaller daughter milk responses in Latin America compared with the US even when herd-year SD was similar.

Animals↗

Effects of age, parity, season of calving, and sire on milk yield of Carora cows in Venezuela.

Age-parity-season of calving, mature equivalent factors were developed for the Carora breed of Venezuela from more than 13,000 244-d milk yield records from the Venezuelan milk recording program from 1975 to 1986. Age-parity-season interactions with parity-age were most important for young cows and seasonal effects most important for old cows. Multiplicative factors were verified as useful to adjust milk yields of Carora and Brown Swiss crossbred cows. Repeatabilities for mature equivalent adjusted milk were .47, .36, and .38 between pairs of repeated records through fourth lactation. Heritability of milk in first lactation by REML procedures was 12% based on 44 Carora sires with 14 effective daughters per sire. Small population size for Carora cattle hinders usefulness and cost effectiveness of progeny testing as the primary investment in genetic gain. Greater potential economy is likely from exploiting the dams of sires genetic pathway.

Age Factors↗

Spiramycin therapy for cryptosporidial diarrhoea in immunocompromised patients.

Spiramycin, 3 g daily, was used to treat immunocompromised patients with chronic diarrhoea due to Cryptosporidium. Most patients treated had acquired immune deficiency syndrome. Among 37 patients evaluated, 28 had a favourable response, defined as a reduction in the daily number of bowel movements to less than 50% of baseline and fewer than five. Twelve of these individuals had Cryptosporidium oocysts eradicated from stool. Spiramycin was well tolerated. These data suggest that spiramycin is effective in alleviating cryptosporidial diarrhoea in some immunocompromised patients and may lead to eradication of cryptosporidial oocysts.

Acquired Immunodeficiency Syndrome↗

Prolongation of hibernation bout duration by continuous intracerebroventricular infusion of melatonin in hibernating ground squirrels.

Melatonin was infused intracerebroventricularly into hibernating golden-mantled ground squirrels (Citellus lateralis) maintained at 5 degrees C in darkness. Continuous infusion at a rate of 0.5 microliter/h was accomplished using an osmotic minipump. The effect of melatonin on hibernation bout duration was determined with reference to the natural trend in bout duration for each animal. At doses of 200 and 400 ng/h, melatonin produced a dose-related increase in bout duration. No effect was observed following control infusions of artificial cerebrospinal fluid or lower doses of melatonin.

Animals↗

In vitro measurements of cholinergic activity in brain regions of hibernating ground squirrels.

High affinity choline uptake (HACU) and choline acetyltransferase (ChAT) activity were measured in synaptosomal P2 fractions from four brain regions in a mammalian hibernator, the golden-mantled ground squirrel. The 14CO2 evolution from [6-14C]glucose was also measured. Comparisons were made across the euthermic (not hibernating) and hibernation state in synaptosomes from cortex (CTX), preoptic area and hypothalamus (POA/HYP), olfactory apparatus (OA), and hippocampus (HPC). HACU was significantly increased in the CTX, from hibernating ground squirrels compared to euthermic animals. ChAT activity was significantly increased in the CTX and OA from hibernating animals. No change in either cholinergic marker was evident for the POA/HYP and HPC. The evolution of 14CO2 from [6-14C]glucose was generally, though not significantly, higher for synaptosomes from euthermic animals compared to hibernating animals. The results are discussed with reference to the involvement of cholinergic mechanisms in the control of hibernation.

Animals↗

Pineal melatonin: circadian rhythm and variations during the hibernation cycle in the ground squirrel, Spermophilus lateralis.

Variations in pineal melatonin content throughout a 24-hour period and during different phases of the hibernation bout cycle were studied in the golden-mantled ground squirrel (Spermophilus lateralis). In addition to pineal melatonin, the circadian variation in the activities of pineal N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT) were also investigated in summer animals maintained at 22 +/- 2 degrees C, on a light:dark (L:D) schedule of 12:12 hr for 1 month (lights on at 08.00 hr). Pineal glands were collected from six animals in each group at 1200, 1600, 2000, 2400, 0200, 0400, and 0800 hr. Changes in pineal melatonin content during the hibernation bout cycle were investigated in ground squirrels housed at 4 +/- .05 degrees C in relative darkness (1.9-3.4 lux; 10:14 LD). Pineal glands were obtained between 12:00 and 18:00 hr from 30 animals during one of three phases of the cycle (deep hibernation, euthermic interbout, and entrance into hibernation). Pineal melatonin was also measured for comparison in six winter euthermic animals that were housed at 22 +/- 2 degrees C, on a L:D schedule of 10:14 hr. Melatonin was measured in individual pineal glands by radioimmunoassay. The daily melatonin rhythm in S. lateralis was characterized by a marked increase in pineal melatonin during the dark phase, in which peak nighttime values were nearly 20-fold greater than daytime basal levels. The daily rhythm for NAT activity paralleled the changes in melatonin, showing a peak activity at 0200 hr that was 45 times greater than mean daytime values.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylserotonin O-Methyltransferase↗

Changes in body temperature and metabolic rate following microinjection of Met-enkephalinamide in the preoptic/anterior hypothalamus of rats.

The effects of Met-enkephalinamide (MET-ENKamide) on brain temperature (Tb) and metabolic rate (MR) were assessed following direct administration into the preoptic/anterior hypothalamus (PO/AH) of freely moving rats. Bilateral microinjections of saline or MET-ENKamide (1-25 micrograms/microliter) were delivered through cannula guide tubes previously implanted in nine animals. Thiorphan, an enkephalinase inhibitor, was microinjected into the PO/AH of two of the animals. All injections were made remotely at an ambient temperature of 22 +/- 1 degree C in a volume of 1 microliter. Measurements of Tb (via a brain-dwelling thermistor) and MR were recorded continuously. The ability of naloxone to antagonize the effects of MET-ENKamide was investigated by fashioning a double-barreled injection cannula to fit within each guide tube; 1 microliter of saline or naloxone (1-10 micrograms) was delivered bilaterally into the PO/AH followed by 1 microliter of MET-ENKamide (25 micrograms) 5-10 min later. PO/AH administration of MET-ENKamide (1-25 micrograms) produced dose-dependent increases in Tb preceded by dose-dependent increases in MR, with a characteristic time course of approximately 30 min. Naloxone antagonized the rise in Tb and MR, either partially or completely, depending on dose. When administered alone, naloxone had no effect on Tb or MR. Microinjection of thiorphan (10 micrograms) into the PO/AH evoked increases in Tb and MR that were similar to those responses induced by MET-ENKamide. These results support a role for endogenous Met-enkephalin in the regulation of Tb in the rat.

Animals↗

Decreases in pineal melatonin content during the hibernation bout in the golden-mantled group squirrel, Spermophilus lateralis.

The role of the pineal gland in modulating the rhythmic bouts of hibernation in the golden-mantled ground squirrel (S. lateralis) was explored by comparing pineal melatonin content in hibernating animals with that of euthermic animals at the same time of year. Significant decreases in pineal melatonin content were found in hibernating versus euthermic animals. In addition, significantly lower values for pineal melatonin were observed in hibernating animals that were sacrificed in the late bout period, just prior to expected spontaneous arousal, as compared to hibernating animals that were sacrificed on the first day of their respective bouts. A strong correlation was evident between pineal melatonin content and the duration of the individual hibernation bout. These data suggest that pineal melatonin may be important in determining the duration of individual bouts of hibernation in this species.

Acclimatization↗

Differential effect of environmental temperature on morphine physical dependence and abstinence.

1) Ambient temperature (Ta) significantly influenced the display of 4 of the 14 naloxone-precipitated withdrawal signs (nesting, flat posture, vocalization, dyspnea) in morphine-dependent, non-hibernating ground squirrels (Citellus lateralis). 2) Analysis of variance performed on the six quantified signs revealed that Ta during withdrawal, but not during the development of physical dependence, was a significant factor in determining the expression of two signs (nesting and vocalization). 3) The interaction between the influence of Ta during the periods of morphine administration and abstinence was a significant factor in determining the expression of nesting behavior, a finding that is consistent with the natural role of nesting as a behavioral thermoregulatory response. 4) We conclude that environmental temperature modulates the expression of selected components of the naloxone-precipitated abstinence syndrome in C. lateralis without exerting a measurable influence on the development of morphine physical dependence itself.

Animals↗

Seasonal variation of morphine physical dependence.

The characteristics of morphine physical dependence in ground squirrels (Citellus lateralis) were examined during each of the four annual seasons. The results showed that this rodent hibernator exhibits a strong and characteristic naloxone-precipitated abstinence syndrome during its non-hibernation state, irrespective of the season. Although qualitatively unchanged throughout the year, the abstinence syndrome showed clear quantitative seasonal differences. These differences were evident in terms of both the number of occurrences of particular signs and the percentage of the morphine-dependent population exhibiting them.

Animals↗