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Biomedical subjects

L I Crawshaw

Publications and source records attributed to L I Crawshaw.

At least 19 recordsLinked to original sources
PubMed1998

Ethanol, body temperature and thermoregulation.

1. The effects of ethanol on body temperature (Tb) and on the regulator of Tb are reviewed. 2. The first section considers how ethanol affects cellular function and how temperature modifies these effects. 3. The next section reviews the effects of ethanol on Tb, covering both disruptive effects and effects on regulatory elements. 4. The final section covers recent work that has made use of genetic techniques to elucidate specific aspects of how ethanol affects temperature regulation.

Animals↗
PubMed1997

Ethanol disrupts and decreases the regulated body temperature differentially in C57BL/6J and DBA/2J mice.

Two inbred mouse strains, C57BL/6J (B6) and DBA/2J (D2), were evaluated for effects of ethanol on thermoregulation. Continuous recording of core temperature (Tc) from undisturbed animals at an ambient temperature (Ta) of 27 degrees C indicated Tc was similar for both strains during active (approximately 38.0 degrees C) and inactive (approximately 36.7 degrees C) periods. Ethanol-injections of 1.5, 2.5, 3.5, and 4.5 g/kg in an environment where Ta rose and fell at 6-min intervals, reaching extremes of 14 and 42 degrees C, produced dose-dependent falls in Tc for both strains. The changes in Ta produced fluctuations in Tc under all conditions. The amplitude of these fluctuations in Tc was used as a measure of physiological disruption. Dose-dependent increases in disruption were found for both strains. At a constant 26 degrees C Ta, ethanol produced dose-related increases in tail temperature. Responses after ethanol administration were different for B6 and D2 mice. The results indicate regulated temperature is similar for B6 and D2 strains. Regulated temperature is decreased more by ethanol for B6 mice, whereas disruption of thermoregulation by ethanol is greater for D2 mice.

Animals↗
PubMed1996

Common genetic determinants of the ataxic and hypothermic effects of ethanol in BXD/Ty recombinant inbred mice: genetic correlations and quantitative trait loci.

Sensitivity and tolerance to ethanol-induced ataxia and hypothermia are determined in part by genetic factors; some genes that affect one of these traits may affect others as well. To test this general hypothesis, we examined hypothermia and two tests of ataxia in the C57BL/6J and DBA/2J inbred mouse stains and in 18 to 25 of their recombinant inbred strains. Genetic correlations among strain mean responses revealed strong positive associations of genetic origin between sensitivity and tolerance for each of the three responses. Furthermore, tolerance to grid test ataxia and tolerance to hypothermia were positively associated. Sensitivity scores across the three responses were uncorrelated. The second method employed to assess genetic correlation was to examine the pattern of genetic locations of quantitative trait loci (QTLs) provisionally identified using genetic mapping procedures. This method identified 3 to 14 QTLs associated with each trait. Within each response, a number of these associations were in common for measures of sensitivity and tolerance; this suggests the existence of several specific genes that exert pleiotropic effects on sensitivity and tolerance. In a result consistent with the analyses of genetic correlations, there was modest evidence for QTLs associated across measures. Some QTLs associated with multiple traits mapped to chromosomal regions where candidate genes (e.g., genes for neurotransmitter receptors) have been mapped. In summary, the analyses presented suggest modest commonality of genetic influence on tolerance to some measures of ataxia and hypothermia, and they strongly support previous data indicating that sensitivity and tolerance to specific effects of ethanol share common genetic determinants.

Animals↗
PubMed1994

Temperature regulation in mice during withdrawal from ethanol dependence.

Temperature regulation during withdrawal from ethanol dependence was studied in mice. Dependence was induced utilizing ethanol vapor inhalation combined with injections of pyrazole, an alcohol dehydrogenase inhibitor. One control group received vehicle (0.9% NaCl); another received pyrazole (68.1 mg/kg) in vehicle. During withdrawal, mice were placed in a thermal gradient, with core temperature (Tc) and preferred temperature (Tpref) continuously recorded for 26 h. During the period of maximal withdrawal severity (4-10 h after removal from ethanol vapor), the withdrawal group was more active than controls. Withdrawal group Tc [36.4 +/- 0.1 (SE) degrees C] was similar to that of NaCl (36.2 +/- 0.1 degrees C) and pyrazole (36.3 +/- 0.2 degrees C) controls. Withdrawal group Tpref (30.5 +/- 0.5 degrees C) was significantly lower than either NaCl (33.5 +/- 0.3 degrees C) or pyrazole (32.9 +/- 0.5 degrees C) controls. Analysis of covariance with activity as covariate indicated that the difference between Tc and Tpref was greater for the withdrawal group and was due to more than increased activity. Mice withdrawing at constant temperature (29.5 degrees C) did not show Tc different from that of controls. These results support the conclusion that regulated body temperature is not altered during withdrawal. We propose that the lower Tpref of withdrawing mice represents a means of dissipating excess heat that is partly generated by the hypermetabolic state accompanying withdrawal from ethanol dependence.

Alcoholism↗
PubMed1994

Quantitative trait loci mapping of genes that influence the sensitivity and tolerance to ethanol-induced hypothermia in BXD recombinant inbred mice.

A recent method allows the identification of the rough genetic map location in mice of genes that exert modest effects on continuously distributed (i.e., quantitative) variables. Sensitivity and tolerance tolerance to the hypothermic effect of ethanol were studied with the purpose of identifying such quantitative trait loci (QTL). Mice from two progenitor inbred strains, C57BL/6J and DBA/2J, and 19 of their recombinant inbred (RI) BXD strains, were given ethanol daily for 3 days. By administering several doses of ethanol and recording multiple postdrug temperatures on the first and third injection day, the authors were able to compute several indices of initial sensitivity and tolerance magnitude in the RI strain battery. The strains differed at most times and doses in their acute reductions in body temperature with respect to their predrug base lines, which indicated genetic control of sensitivity to ethanol-induced hypothermia. The areas under the curve (which describes the initial hypothermic response over time), a measure that reflects both the maximal hypothermia achieved and the duration of total hypothermic response, also differed. The strains also differed in the magnitude of the tolerance developed to ethanol-induced hypothermia. Genetic determinants of sensitivity (and tolerance) to different doses of ethanol were primarily independent, although genetic sensitivity and tolerance to the intermediate (2- and 3-g/kg) doses were significantly correlated.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Genetic selection alters thermoregulatory response to ethanol.

The present study examined the effect of ethanol on the regulated temperature of two lines of mice selected in replicate for a smaller (HOT1 and HOT2) or greater (COLD1 and COLD2) decline in rectal temperature after IP ethanol. Mice were implanted with indwelling telemetry devices for remote monitoring of internal temperature and trained in a temperature gradient (8-40 degrees C). Both internal and selected temperature were tracked and recorded with a computer after injections of NaCl or various doses of ethanol. All animals responded similarly to control injections, with a transient rise in body temperature. After an effective dose of ethanol, mice showed clear evidence of a regulated decline in body temperature, as evidenced by selection of low temperatures in the gradient at the same time internal temperatures were falling. COLD mice were more sensitive than HOT mice; this was apparent in both replicates of the selected lines, indicating that a difference in the CNS regulator of body temperature has been selected for in these animals.

Animals↗
PubMed1992

Effective loci and roles of acetylcholine in temperature regulation of goldfish.

Microinjections of acetylcholine (ACh) and carbachol were made into discrete forebrain loci in goldfish (Carassius auratus) to evaluate the importance of cholinergic mechanisms for behavioral thermoregulation. Injections of 5, 10, 25, and 50 micrograms ACh into the far anterior nucleus preopticus periventricularis (NPP) (R. Peter and V. Gill. J. Comp. Neurol. 159: 69-102, 1975) and immediately adjacent ventral telencephalon led to consistent dose-dependent decrease in selected temperature. No effect was observed following injections of 2 micrograms ACh or 0.7% NaCl. Injections of ACh into a different portion of the ventral telencephalon led to increases in the selected temperature. Lower doses of carbachol (0.5 and 1.0 micrograms) injected into the NPP produced decreases in selected temperature similar to the highest doses of ACh. Injections of ACh into loci other than those mentioned above either had no thermoregulatory effect or had lesser thermoregulatory effects which, in comparison with injections into the most effective sites, were inconsistent and required larger doses to obtain. The site where cholinergic stimulation led to decreases in the selected temperature exactly overlapped the effective site of ethanol hypothermia in the goldfish.

Acetylcholine↗
PubMed1989

The effects of dopamine on temperature regulation in goldfish.

Microinjections of dopamine (DA) were made into specific forebrain loci in goldfish (Carassius auratus: 40-85 g) to study the involvement of DA in behavioral thermoregulation. Injections of 25, 50, 100 and 250 ng DA into the anterior aspect of the nucleus preopticus periventricularis (NPP) led to consistent, dose-dependent decreases in selected temperature. Minor decreases or no effect on selected temperature was observed following injections of 5 or 10 ng DA. Injections of the control solution were without effect. Injections of DA into other forebrain loci, including the posterior half of the NPP, either had no thermoregulatory effect or had minor thermoregulatory effects which, in comparison, to injections into the most effective sites, were inconsistent and required larger doses to obtain. The decrease in selected temperature following injections of 100 ng DA into the anterior NPP was blocked by haloperidol, a dopaminergic antagonist, but not by phentolamine, a noradrenergic antagonist. Injections of haloperidol alone resulted in a minor, but statistically significant, increase in selected temperature. The most sensitive DA sites lie caudal to the sites most sensitive to norepinephrine within the anterior NPP. DA acts on the dopaminergic receptors of central thermoregulatory neurons in the anterior NPP of goldfish. These receptors appear to mediate behavioral responses to excessively warm environments.

Animals↗
PubMed1989

The effect of ethanol on behavioral temperature regulation in mice.

Mice were injected with 20% ethanol in 0.9% NaCl, or with 0.9% NaCl without ethanol during sessions of behavioral thermoregulation in a tubular temperature gradient (ambient temperature range approximately 9-38 degrees C). Internal temperature was monitored with an implanted telemetry device. An imaging system recorded the position (selected temperature) of the mouse within the gradient every 5 sec. A dose of either 2.25 or 2.60 g ethanol/kg body wt. produced significantly lower body temperatures than control (NaCl) injections. The 2.60 g/kg dose produced significantly lower selected temperatures than either the NaCl or 2.25 g/kg injections. Doses of 2.75 g ethanol/kg and above incapacitated the mice, precluding accurate behavioral thermoregulation. Utilizing a thermoregulatory index to compare the responses following experimental and control injections indicated that 2.25 or 2.60 g ethanol/kg leads to a decrease in the regulated temperature of mice.

Animals↗
PubMed1989

Intracranial ethanol and ambient anoxia elicit selection of cooler water by goldfish.

Goldfish were either subjected to anoxia for 5 h at 10 degrees C, normoxia for 5 h at 10 degrees C, or were implanted with an intracranial microinjection cannula. All groups were subsequently tested in a temperature gradient. The previously anoxic goldfish selected cooler temperatures (12.8 +/- 1.0 degrees C; mean +/- SE) than the corresponding normoxic control group (17.5 +/- 0.7 degrees C) for the first 20 min in the gradient. Intracranial microinjections of 0.0475 ng ethanol in 0.2 microliter 0.7% NaCl led to the immediate selection of water 8.7 +/- 1.5 degrees C below that of base-line levels, whereas control animals injected with 0.7% NaCl selected water 0.9 +/- 1.0 degree C cooler. Increased effects were obtained with higher concentrations of ethanol. The effective site was limited to the anterior aspect of the nucleus preopticus periventricularis; injections into 54 other loci were without effect. Goldfish tolerate anoxia by the conversion of lactate to ethanol, which diffuses across the gills. As the lost ethanol cannot be oxidatively metabolized, this process is energetically inefficient. Because the concentration of the ethanol injections was considerably lower than reported ethanol concentrations in the tissues of anoxic goldfish, endogenously produced ethanol may have induced the selection of cooler water by the anoxic goldfish. This alteration in thermoregulatory behavior would lead to a lower metabolic rate, significantly increasing survival time during anoxia.

Animals↗
PubMed1988

The effect of ethanol on temperature selection in the goldfish, Carassius auratus.

The effect of ethanol on behavioral thermoregulation in the goldfish, Carassius auratus, was studied by adding ethanol to a horizontal aquatic temperature gradient which allowed each fish to select its preferred temperature within a range of about 9 degrees C to 33 degrees C. Alternating exposure to 1.0% (v/v) ethanol and water showed that fish (10 to 15 g) responded to ethanol by selecting lower temperatures. Onset and disappearance of the effect occurred within 10 min of exposure to or removal from ethanol. Fish exposed to 1.0% ethanol for 3 hr did not show acute tolerance. When fish were exposed to increasing concentrations of ethanol from 0.0% to 1.7%, the lowest concentration to elicit a response was 0.5% ethanol. The magnitude of the response plateaued at 0.7% ethanol. At this concentration and above, selected temperatures remained about 2 degrees C below temperatures selected by controls. Because thermoregulatory responses of fish are behavioral and relatively easy to observe and quantify, goldfish offer a useful model for the study of ethanol effects on central nervous system control of thermoregulation. Ethanol produces a prompt, stable, and reproducible depression of selected temperature by lowering the thermoregulatory set point in the goldfish.

Animals↗
PubMed1988

Adrenoceptors and temperature regulation in goldfish.

In goldfish, microinjections of norepinephrine (NE) into the anterior aspect of the nucleus preopticus periventricularis result in dose-dependent decreases in selected temperature (21). To determine the characteristics of the adrenoceptors involved in this response, noradrenergic antagonists were injected 10 min before an injection of 50 ng norepinephrine. In comparison to control injections, injections of 50 ng phentolamine, an alpha-antagonist, significantly attenuated the effect of NE. In contrast, 50 ng propranolol, a beta-antagonist, produced a nonsignificant attenuation. These antagonists injected by themselves had no thermoregulatory effect. For noradrenergic agonists, thermoregulatory effects comparable to a dose of 10-25 ng NE were obtained at the following doses (in microgram): 1.0 clonidine (alpha 2), 5.0 phenylephrine (alpha 1), and 25 isoproterenol (beta). In fish, both alpha 1 and alpha 2-adrenoceptors appear to subserve the NE-induced decrease in selected temperature. Because antagonists injected by themselves do not have a thermoregulatory effect, NE may not have a role in the short-term regulation of body temperature in fish but rather may modulate this system in response to altered environmental conditions.

Animals↗
PubMed1987

Significance of vessel size and type in vascular heat transfer.

This study was undertaken to gain a better understanding of the fundamental mechanisms of micro- and macrovascular heat transfer by experimentally identifying those vessels most important in the process. Tissue temperature fields around thermally nonequilibrated vessels were determined using a small temperature sensor that was guided through the rabbit thigh to generate a detailed temperature map. The measurements revealed that the lower limit of vessel size for thermal nonequilibration was 100 microns for arteries and 400 microns for veins. Local temperature fields were found around four of the five (80%) arteries that were greater than 300 microns in diameter but in only 3 of the 12 (25%) veins greater than 400 microns. These experimental results are in good agreement with previously published theoretical studies (5) in which it was concluded that thermal equilibration in the branching countercurrent vascular network of the rabbit limb occurs in vessels an order of magnitude larger than the capillaries. In those studies the smallest vessels capable of carrying heat were predicted to be 50 microns ID with the major blood tissue heat exchange occurring in vessels greater than 100 micron ID. These findings contrast with the view that most heat transfer occurs in the capillaries and suggest that vascular heat transfer analysis must take into account the vascular architecture of the 50- to 1,000-micron vessels where most heat transfer occurs.

Animals↗
PubMed1987

Thermoregulatory effects of intracranial norepinephrine injections in goldfish.

Cannulas were implanted into forebrain loci of goldfish (Carassius auratus; 45-90 g) to determine the effects and site of action of intracranial norepinephrine (NE) injections on behavioral thermoregulation. Following 30 min in a thermal gradient, implanted fish were injected with norepinephrine-bitartrate salt (2.5-500 ng NE) in 0.2 microliter 0.7% NaCl. Injections of 5, 10, 25, and 50 ng NE into the anterior aspect of the nucleus preopticus periventricularis (NPP, Ref. 25) led to consistent dose-dependent decreases in selected temperature (Tsel). No effect on Tsel was observed following injections of 2.5 ng NE or control injections of 100 ng tartaric acid. The effects of injections into other loci, including intraventricular injections, were dependent on the dose and proximity to the anterior NPP; at sites adjacent to the anterior NPP, larger doses were required, and the effects became inconsistent. At sites further removed, no effect on Tsel was observed. Included in this category were more caudal sites within the NPP and the nucleus preopticus. We postulate that in fish the anterior NPP is an important locus for thermoregulatory integration and that increased release of NE in this area leads to the selection of cooler water.

Animals↗
PubMed1984

Low-temperature dormancy in fish.

The importance of low ambient temperature in the physiology of winter dormancy was studied in the brown bullhead (Ictalurus nebulosus) and the largemouth bass (Micropterus salmoides). The bullheads frequently entered a sleep-like state at low temperatures; the likelihood of being aroused from this state was inversely proportional to the ambient temperature. Spontaneous activity for both species was relatively constant from 17 to 7 degrees C; at lower temperatures activity decreased. The selected temperature was lowered in both species as a consequence of acclimation to 3 degrees C; if given the opportunity, fish of both species moved to temperatures above 25 degrees C within 1 day in spite of the consequent acid-base and metabolic imbalances. In bass, food intake was very low for acclimation temperatures of 8 degrees C and below; at higher temperatures the relationship between food intake and acclimation temperature required 4 wk to stabilize. Quiescent brown bullheads exhibited discontinuous breathing. Alteration of brain temperature with implanted thermodes indicated that the main locus of control of this breathing pattern is in the medulla; lesser influences emanate from the anterior hypothalamus and the midbrain. Metabolism was measured at a series of acclimation temperatures between 3 and 17 degrees C for both species. No evidence of a discontinuous function (metabolic shutdown) was seen for either species.

Animals↗
PubMed1982

Metabolic and acid-base changes during selection of warmer water by cold-acclimated fish.

Largemouth bass (Micropterus salmoides) acclimated to 3 degrees C were placed in a thermal gradient. The bass selected the final thermal preferendum of 28 degrees C in about 18 h. The movement into warmer water was initially rapid but became progressively slower. 2) Other bass were acclimated to 8 degrees C, cannulated in the dorsal aorta, and placed in a temperature-controlled chamber. Oxygen uptake, blood pH, and total CO2 were measured as the chamber temperature was increased to 28 degrees C following a time course similar to that followed by bass in the gradient. 3) Oxygen uptake was always elevated above the resting level, and this elevation increased as higher temperatures were encountered. 4) Just prior to placement in the chamber the pH of the arterial blood was 7.98 +/- 0.05 (mean +/- SE). As the temperature was increased neither the pH nor the total CO2 content of the blood exhibited major changes. At temperatures between 26 and 28 degrees C, the pH (8.01 +/- 0.03) was about 0.3 pH units above predicted normal values. 5) During the return to the final thermal preferendum fish experience overall metabolic rates and extracellular acid-base levels that deviate progressively farther from normal resting levels. Neither factor appears likely to be the major determinant of the behavioral response.

Acclimatization↗