Genetically determined differences in ethanol sensitivity influenced by body temperature during intoxication

The present study investigated the importance of body temperature during intoxication in mediating differences between five inbred strains of mice (C57BL/6J; BALB/cJ; DBA/2J; A/HeJ; 129/J) in their acute sensitivity to the hypnotic effects of ethanol. Mice exposed to 22 degrees C after ethanol injection became hypothermic and exhibited statistically significant differences between strains in rectal temperatures at the return of the righting reflex (RORR), duration of loss of the righting reflex (LORR), and blood and brain ethanol concentrations at RORR. Exposure to 34 degrees C after injection offset ethanol-hypothermia and markedly reduced strain-related differences in rectal temperatures and blood and brain ethanol concentrations at RORR. Brain ethanol concentrations at RORR were significantly lower in C57, BALB, DBA and A/He mice exposed to 34 degrees C compared to mice exposed to 22 degrees C during intoxication suggesting that offsetting hypothermia increased ethanol sensitivity in these strains. Taken with previous in vitro studies, these results suggest that genetically determined differences in acute sensitivity to the behavioral effects of ethanol reflect differences in body temperature during intoxication as well as differences in sensitivity to the initial actions of ethanol at the cellular level.     

d-pipecolic acid inhibits ethanol tolerance in mice

The effects of graded doses ofd-pipecolic acid (0.005–5 g/animals s.c.) on tolerance to the hypothermic effect of ethanol (4 g/kg i.p.) were investigated in mice.d-pipecolic acid itself did not change the core temperature or the acute hypothermic response to a single dose of ethanol. Repeatedd-pipecolic acid administration, however, blocked the development of tolerance to the hypothermic effect of ethanol. The development of tolerance could be observed in the control group. It is assumed thatd-pipecolic acid is capable of counteracting the tolerance effect of ethanol.     

Decrease of core body temperature in mice by dehydroepiandrosterone

Dietary dehydroepiandrosterone (DHEA) reduces food intake in mice, and this response is under genetic control. Moreover, both food restriction and DHEA can prevent or ameliorate certain diseases and mediate other biological effects. Mice fed DHEA (0.45% w/w of food) and mice pair-fed to these mice (food restricted) for 8 weeks were tested for changes in body temperature. DHEA was more efficient than food restriction alone in causing hypothermia. DHEA injected intraperitoneally also induced hypothermia that reached a nadir at 1 to 2 hr, and slowly recovered by 20 to 24 hr. This effect was dose dependent (0.5-50 mg). Each mouse strain tested (four) was susceptible to this effect, suggesting that the genetics differ for induction of hypophagia and induction of hypothermia. Because serotonin and dopamine can regulate (decrease) body temperature, we treated mice with haloperidol (dopamine receptor antagonist), 5,7-dihydroxytryptamine (serotonin production inhibitor), or ritanserin (serotonin receptor antagonist) prior to injection of DHEA. All of these agents increased rather than decreased the hypothermic effects of DHEA. DHEA metabolites that are proximate (5-androstene-3beta, 17beta-diol and androstenedione) or further downstream (estradiol-17beta) were much less effective than DHEA in inducing hypothermia. However, the DHEA analog, 16alpha-chloroepiandrosterone, was as active as DHEA. Thus, DHEA administered parentally seems to act directly on temperature-regulating sites in the body. These results suggest that DHEA induces hypothermia independent of its ability to cause food restriction, to affect serotonin or dopamine functions, or to act via its downstream steroid metabolites.     

Effect of body temperature on acute ethanol toxicity

We studied the effect of elevated rectal temperature on ethanol toxicity and the effect of ethanol on the mean lethal temperature (LT50). The rectal temperature was maintained at a preselected level for 4 h. Ethanol (23% w/v) was injected i.p. In control mice anesthetized with pentobarbital, the 4 h LT50 was 41.8 ± 0.1°C (mean ± standard error). In mice which had received a non-lethal ethanol dose (6 g/kg), the LT50 was decreased to 39.0 ± 0.2°C (p< 0.001). In control mice, whose temperature dropped, the 4 h ethanol LD50 was 8.5 ± 0.8 g/kg. If the rectal temperature of the mice was maintained instead at a maximum of 38.5 – 40°C, the LD50 was decreased to 5.7 ± 0.8 g/kg (p < 0.02). The results show that ethanol increases the susceptibility of mice to hyperthermic damage, and conversely, that hyperthermia increases the toxicity of ethanol.     

Chronic dependence with a sustained ethanol release implant in mice

A new parenteral form of chronic ethanol exposure to mice is described. The Sustained Ethanol Release Tube (SERT) is a simple, inexpensive, easily-constructed silastic tube which is implanted under the skin of the animal's back. Release characteristics of the tube for 95% v/v ethanol are ideal for maintaining blood alcohol levels initiated by low ip. loading doses of ethanol. With SERT refills every 12 hr and appropriate booster doses, mice can be made physically dependent upon ethanol in 4 days. There is no tissue damage around the SERT or in the peritoneum, and weight loss in the treated mice is minimal, compared to control isolated and saline-exposed mice. The device may be useful for studying the release of other solvents, and may be adaptable for use in larger animals.     

Forskolin promotes the development of ethanol tolerance in 6-hydroxydopamine-treated mice

Partial depletion of brain norepinephrine by 6-hydroxydopamine prevents the development of functional tolerance to ethanol in mice. This blockade of tolerance development was overcome by daily intracerebroventricular injections of forskolin. These results suggest that interaction of norepinephrine with post-synaptic beta-adrenergic receptors, and activation of adenylate cyclase, is important for the development of ethanol tolerance. Interaction of norepinephrine with alpha 1-adrenergic receptors may be less crucial, since treatment with a phorbol ester activator of protein kinase C did not restore the development of tolerance in mice treated with 6-hydroxydopamine. The importance of the beta-adrenergic receptor-coupled adenylate cyclase system for development of ethanol tolerance, in addition to its previously-reported role in long-term potentiation, suggests that this system may influence neuroadaptive processes in general.     

Brain levels and turnover rates of presumptive neurotransmitters as influenced by administration and withdrawal of ethanol in mice

—Effects of acute or chronic administration of ethanol and its withdrawl on the steady-state levels and turnover rates of certain neurotransmitters have been investigated in mice. The influence of long-term administration of ethanol on the activities of enzymes involved in the metabolism of these transmitters has also been studied. Acute administration of ethanol or acetaldehyde or chronic administration of ethanol resulted in a decrease in the cerebral contents of acetylcholine, acetylCoA and CoA. Brain levels of 5-hydroxytryptamine, norepinephrine and choline remained unchanged after acute administration of ethanol. However, chronic administration of ethanol resulted in a decrease in the norepinephrine content without significantly affecting 5-hydroxytryptamine or choline contents. Cerebral levels of γ-aminobutyric acid increased with both acute or chronic administration of ethanol. The total incorporation of [³H]choline into acetylcholine in brain was depressed upon acute administration of ethanol. After withdrawal of ethanol for one day cerebral levels of norepinephrine returned to normal; however, γ-aminobutyric acid and acetylcholine returned to normal levels at 2 and 4 days after ethanol withdrawal, respectively. Pretreatment of mice with pyrazole, an inhibitor of alcohol dehydrogenase, prevented the ethanol-induced decrease in cerebral acetylcholine levels. The activities of cerebral choline acetyltransferase and glutamic decarboxylase were decreased after 2 weeks of chronic ethanol administration. However, the activities of acetyl cholinesterase and GABA-transaminase remained unaffected after 2 weeks of ethanol treatment     

Effects of ambient temperature on adaptive thermogenesis during maintenance of reduced body weight in mice

We showed previously that, at ambient room temperature (22°C), mice maintained at 20% below their initial body weight by calorie restriction expend energy at a rate below that which can be accounted for by the decrease of fat and fat-free mass. Food-restricted rodents may become torpid at subthermoneutral temperatures, a possible confounding factor when using mice as human models in obesity research. We examined the bioenergetic, hormonal, and behavioral responses to maintenance of a 20% body weight reduction in singly housed C57BL/6J +/+ and Lep(ob) mice housed at both 22°C and 30°C. Weight-reduced high-fat-fed diet mice (HFD-WR) showed similar quantitative reductions in energy expenditure-adjusted for body mass and composition-at both 22°C and 30°C: -1.4 kcal/24 h and -1.6 kcal/24 h below predicted, respectively, and neither group entered torpor. In contrast, weight-reduced Lep(ob) mice (OB-WR) housed at 22°C became torpid in the late lights-off period (0200-0500) but did not when housed at 30°C. These studies indicate that mice with an intact leptin axis display similar decreases in "absolute" energy expenditure in response to weight reduction at both 22°C and 30°C ambient temperature. More importantly, the "percent" decrease in total energy expenditure observed in the HFD-WR compared with AL mice is much greater at 30°C (-19%) than at 22°C (-10%). Basal energy expenditure demands are ～45% lower in mice housed at 30°C vs. 22°C, since the mice housed at thermoneutrality do not allocate extra energy for heat production. The higher total energy expenditure of mice housed at 22°C due to these increased thermogenic demands may mask physiologically relevant changes in energy expenditure showing that ambient temperature must be carefully considered when quantifying energy metabolism in both rodents and humans.     

Development of ethanol tolerance in Clostridium thermocellum: effect of growth temperature.

The growth of Clostridium thermocellum ATCC 27405 and of C9, an ethanol-resistant mutant of this strain, at different ethanol concentrations and temperatures was characterized. After ethanol addition, cultures continued to grow for 1 to 2 h at rates similar to those observed before ethanol was added and then entered a period of growth arrest, the duration of which was a function of the age of inocula. After this period, cultures grew at an exponential rate that was a function of ethanol concentration. The wild-type strain showed a higher energy of activation for growth than the ethanol-tolerant derivative. The optimum growth temperature of the wild type decreased as the concentration of the ethanol challenge increased, whereas the optimum growth temperature for C9 remained constant. The results are discussed in terms of what is known about the effects of ethanol and temperature on membrane composition and fluidity.     

System of ethanol and acetaldehyde metabolism in the rat liver during the development of ethanol tolerance

Following daily intraperitoneal injections of ethanol at a dose of 3.5 g/kg rats developed tolerance to its hypnotic action, which was manifested in a drastic decrease of ethanol--induced sleep time and the number of animals sleeping more than 60 min. In the liver, this process was characterized by an elevated alcohol dehydrogenase activity and a decreased aldehyde dehydrogenase one, whereas that of MEOS remained unchanged.     

Functional ethanol tolerance in Drosophila

In humans, repeated alcohol consumption leads to the development of tolerance, manifested as a reduced physiological and behavioral response to a particular dose of alcohol. Here we show that adult Drosophila develop tolerance to the sedating and motor-impairing effects of ethanol with kinetics of acquisition and dissipation that mimic those seen in mammals. Importantly, this tolerance is not caused by changes in ethanol absorption or metabolism. Rather, the development of tolerance requires the functional and structural integrity of specific central brain regions. Mutants unable to synthesize the catecholamine octopamine are also impaired in their ability to develop tolerance. Taken together, these data show that Drosophila is a suitable model system in which to study the molecular and neuroanatomical bases of ethanol tolerance.     

Changes in temperature tolerance ofBalanus balanoides during its life-cycle

Summary 1. The barnacleBalanus balanoides exhibits little seasonal variation in upper lethal temperatures in North Wales.2. There are marked seasonal changes in resistance to sub-zero temperatures, the lower lethal varying from –6.0° C in June to –17.6° C in January.3. Exceptional tolerance to cold is acquired between December and January and is lost between February and April. Although these dates coincide with oviposition and naupliar liberation respectively, it was found that cold tolerance did not necessarily depend upon, or accompany, the normal breeding cycle.4. Cold tolerance was not acquired by animals kept cold in the laboratory during winter, nor was it lost in animals kept in the laboratory during spring. There was no evidence that changes in nutrition or in the light régime led to loss of cold tolerance.5. The cyprids were considerably less resistant to both high and low temperatures than the overwintering adults and the late-stage embryos. There was a marked increase in resistance at metamorphosis.6. The appearance of cold tolerance in the adult coincides with a period of physiological hibernation, involving loss of certain tissues, diminished feeding activity, respiration and biosynthesis. The metabolic inactivity of the animal may be a factor promoting the greatly increased tolerance to cold that we have observed, while the composition of the body fluids may also be modified during the winter in such a way as to protect the tissues.

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Veränderungen der Temperaturtoleranz vonBalanus balanoides während seines Lebenszyklus

Kurzfassung In Nordwales weisen die oberen Letaltemperaturen des CirripediersB. balanoides nur geringe jahreszeitliche Variationen auf. Jedoch treten je nach der Jahreszeit merkbare Resistenzveränderungen bei Temperaturen unter Null auf, wobei die untere Letaltemperatur von –6,0° C im Juni bis zu –17,6° C im Januar schwankt. Eine außergewöhnlich starke Kältetoleranz wird in der Zeit von Dezember und Januar erworben und zwischen Februar und April wieder verloren. Obwohl diese Zeitspanne mit der Oviposition beziehungsweise dem Schlüpfen der Nauplien zusammenfallen, konnte festgestellt werden, daß die Kältetoleranz nicht notwendigerweise vom Brutzyklus abhing oder diesen begleitete. Unter Laboratoriumsbedingungen wurde von kalt gehaltenen Tieren eine Kälteresistenz nicht erworben, auch ging diese bei Tieren, die während des Frühlings im Labor verblieben, nicht verloren. Es ließ sich nicht beweisen, daß Veränderungen in der Ernährung oder Änderungen in der Tageslänge zu einem Verlust der Kälteresistenz führen. Die Cypriden waren wesentlich weniger widerstandsfähig, sowohl gegenüber hohen wie niedrigen Temperaturen, als überwinternde Adulte und die ältesten Embryostadien. Während der Metamorphose zeigte sich eine merkliche Erhöhung der Temperaturresistenz. Das Auftreten der Kälteresistenz beim Adultus fiel mit einer Periode physiologischen Winterschlafs zusammen, wobei gewisse Gewebe reduziert wurden und Nahrungsaufnahme, Atmung und biosynthetische Aktivität nachließen. Dieser stoffwechselphysiologische Aktivitätsrückgang könnte ein Faktor sein, der die beobachtete erhöhte Kältetoleranz fördert. Außerdem wird möglicherweise auch die Zusammensetzung der Körperflüssigkeiten während des Winters so verändert, daß die Gewebe geschützt werden.

     

Iron acquisition by phytosiderophores contributes to cadmium tolerance

Based on the ability of phytosiderophores to chelate other heavy metals besides iron (Fe), phytosiderophores were suggested to prevent graminaceous plants from cadmium (Cd) toxicity. To assess interactions between Cd and phytosiderophore-mediated Fe acquisition, maize (Zea mays) plants were grown hydroponically under limiting Fe supply. Exposure to Cd decreased uptake rates of 59Fe(III)-phytosiderophores and enhanced the expression of the Fe-phytosiderophore transporter gene ZmYS1 in roots as well as the release of the phytosiderophore 2'-deoxymugineic acid (DMA) from roots under Fe deficiency. However, DMA hardly mobilized Cd from soil or from a Cd-loaded resin in comparison to the synthetic chelators diaminetriaminepentaacetic acid and HEDTA. While nano-electrospray-high resolution mass spectrometry revealed the formation of an intact Cd(II)-DMA complex in aqueous solutions, competition studies with Fe(III) and zinc(II) showed that the formed Cd(II)-DMA complex was weak. Unlike HEDTA, DMA did not protect yeast (Saccharomyces cerevisiae) cells from Cd toxicity but improved yeast growth in the presence of Cd when yeast cells expressed ZmYS1. When supplied with Fe-DMA as a Fe source, transgenic Arabidopsis (Arabidopsis thaliana) plants expressing a cauliflower mosaic virus 35S-ZmYS1 gene construct showed less growth depression than wild-type plants in response to Cd. These results indicate that inhibition of ZmYS1-mediated Fe-DMA transport by Cd is not related to Cd-DMA complex formation and that Cd-induced phytosiderophore release cannot protect maize plants from Cd toxicity. Instead, phytosiderophore-mediated Fe acquisition can improve Fe uptake in the presence of Cd and thereby provides an advantage under Cd stress relative to Fe acquisition via ferrous Fe.     

Onion fly oviposition as influenced by soil temperature

A direct causal relationship was demonstrated between soil temperature and insect ovipositional propensity. When ovipositional substrates (soils) at 5, 15, 22, 30, 35, and 40°C were presented in multiple treatment (choice) tests with air temperature at 15 or 22°C, onion flies, Delia antiqua (Meigen) (Diptera: Anthomyiidae), laid the most eggs in the 22°C substrate. Only 50 eggs were laid when air temperature was increased to 30°C, as compared to 454 and 1128 eggs at 22 and 15°C, respectively. Thus, an air temperature of 30°C appears to be near the upper limit of onion fly ovipositional activity. The numbers of flies observed (counts taken every 15 min) on substrates ranging from 15 to 40°C were not significantly different. Reduced alightment/arrestment does not explain reduced oviposition on the warmer substrates; however, it may partly explain reduced oviposition on 5°C substrates. The range of substrate temperatures facilitating substantial oviposition was narrower than that eliciting alightment/arrestment on the substrate. The ca. 20°C ovipositional optimum corresponds well with temperatures favoring egg survival and development.

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Résumé La température du sol est réglée, dans les pondoirs de D. antiqua, par un thermoblock, tandis que toutes les autres variables, associées au succédané d'oignon servant de stimulus de ponte, sont maintenues constantes. Une relation causale entre température du sol et activité de ponte est mise en évidence. Quand il y a choix entre des substrats de ponte à 5, 15, 22, 30 et 40°C, avec une température de l'air de 22°C, les mouches pondent surtout dans le substrat à 22°C. L'optimum thermique est de 20°C quand la température de l'air est abaissée à 15°C. La ponte n'est que de 50 ufs quand la température de l'air est portée à 30°C, contre respectivement 454 et 1128 ufs à 22 et 15°C. Ainsi, une température de l'air de 30°C paraît proche de la limite supérieure de l'activité de ponte de D. antiqua. Le nombre de mouches observées sur le substrat (toutes les 15 min.) ne varie pas significativement quand la température du substrat est entre 15 et 40°C. La gamme de températures provoquant la fixation sur le substrat est plus large que celle des températures provoquant une ponte importante. L'optimum de 20°C correspond bien aux températures favorables à la survie et à la croissance de D. antiqua.Ce travail montre l'effet important de facteurs abiotiques sur l'acceptation de la plante-hôte.

     

Effects of acetic acid on the temperature profile of ethanol tolerance inSaccharomyces cerevisiae

Summary In a strain ofSaccharomyces cerevisiae, acetic acid at concentrations up to 1% (v/v) depressed the tolerance to added ethanol, from 11% (v/v) down to zero, and simultaneously narrowed the temperature range of growth from 3–42°C to 19–26°C. In addition, acetic acid shifted the associative temperature profile of growthand death to lower temperatures, and depressed the growth yield on glucose.