Effects of ethanol on urinary arginine vasopressin excretion in two rat strains selected for their different ethanol preferences

The effects of ethanol on urinary excretion of arginine vasopressin (AVP), sodium, and potassium were investigated in two rat strains specially selected for their different alcohol preferences. The alcohol preferring (AA) strain excreted more AVP and the water preferring (ANA) strain more urine and sodium during six hours after ethanol intubation (2.4 g/kg b.w.; 20% v/v). The data is insufficient to establish a causal relationship between differences in water and electrolyte metabolism and voluntary ethanol consumption.     

Urine sodium, potassium and osmolality in two rat strains selected for their different ethanol preferences

Urine sodium, potassium and osmolality were investigated during water and ethanol diuresis in two rat strains, AA and ANA, which drink voluntarily different amounts of ethanol. At the start of each experiment the rats were in a positive water balance. During ethanol intoxication the AA strain excreted more urine than the ANA strain. In ethanol experiments the osmolality of the urine was higher in the AA strain than in the ANA strain. With ethanol amounts of 2.4 g/kg body weight and 4.8 g/kg of body weight, urinary sodium and potassium output was greater in AA rats than ANA rats. When only water was introduced urine volumes and the excretion of sodium and potassium during 180 min were greater in ANA males than in AA males.     

Effects of ethanol on structural parameters of rat brain membranes: relationship to genetic differences in ethanol sensitivity

Equine leukoencephalomalacia (ELEM) affected 6 of 10 pleasure horses in adjacent paddocks at a boarding facility. Four of the 6 affected horses died or were euthanized. Two of 3 horses presented for treatment survived with complete resolution of clinical signs. Treatment was primarily supportive. Dimethyl sulfoxide, dexamethasone, flunixin meglumine and thiamine were administered as anti-inflammatory agents and to decrease or prevent cerebral edema. Fusarium monileforme was cultured from ear corn fed the affected horses. Fumonisin B1, B2 and B3 were isolated.     

Spurious associations in unreplicated selected lines

INTRODUCTION: Shocks during the vulnerable period of the cardiac cycle induce ventricular fibrillation (VF) if their strength is above the VF threshold (VFT) and less than the upper limit of vulnerability (ULV). However, the range of shock strengths that constitutes the vulnerable zone and the corresponding range of coupling intervals have not been defined in humans. The ULV has been proposed as a measure of defibrillation because it correlates with the defibrillation threshold (DFT), but the optimal coupling interval for identifying it is unknown. METHODS AND RESULTS: We studied 14 patients at implants of transvenous cardioverter defibrillators. The DFT was defined as the weakest shock that defibrillated after 10 seconds of VF. The ULV was defined as the weakest shock that did not induce VF when given at 0, 20, and 40 msec before the peak of the T wave or 20 msec after the peak in ventricular paced rhythm at a cycle length of 500 msec. The VFT was defined as the weakest shock that induced VF at any of the same four intervals. To identify the upper and lower boundaries of the vulnerable zone, we determined the shock strengths required to induce VF at all four intervals for weak shocks near the VFT and strong shocks near the ULV. The VFT was 72 +/- 42 V, and the ULV was 411 +/- V. In all patients, a shock strength of 200 V exceeded the VFT and was less than the ULV. The coupling interval at the ULV was 19+/- 11 msec shorter than the coupling interval at the VFT (P < 0.001). The vulnerable zone showed a sharp peak at the ULV and a less distinct nadir at the VFT. A 20-msec error in the interval at which the ULV was measured could have resulted in underestimating it by a maximum of 95 +/- 31 V. The weakest shock that did not induce VF was greater for the shortest interval tested than for the longest interval at both the upper boundary (356 +/- 108 V vs 280 +/- 78 V; P < 0.01) and lower boundary (136 +/- 68 msec vs 100 +/- 65 msec; P < 0.05). CONCLUSIONS: The human vulnerable zone is not symmetric with respect to a single coupling interval, but slants from the upper left to lower right. Small differences in the coupling interval at which the ULV is determined or use of the coupling interval at the VFT to determine the ULV may result in significant variations in its measured value. An efficient strategy for inducing VF would begin by delivering a 200-V shock at a coupling interval 10 msec before the peak of the T wave.     

Pharmacologic actions of subtype-selective and novel GABAergic ligands in rat lines with differential sensitivity to ethanol

Alcohol-nontolerant (ANT) rats, produced by selective breeding for high sensitivity to motor-impairing effects of ethanol, have a point mutation in the cerebellar gamma-aminobutyric acid type A (GABAA) receptor alpha 6 subunit, which has been proposed to underlie enhanced sensitivity to benzodiazepine agonists as well. We compared ANT and alcohol-tolerant (AT) rats using behavioral and neurochemical methods to assess the significance of alpha 6- and non alpha 6-containing GABAA receptor subtypes. Motor performance in a tilting plane test was largely unaffected by a type I benzodiazepine receptor-preferring agonist, zolpidem [1-10 mg/kg, intraperitoneally (IP)], partial benzodiazepine agonists bretazenil and ZG-63 (both at 40 mg/kg, IP), and a novel broad-spectrum anticonvulsant loreclezole (40 mg/kg, IP) in both ANT and AT rats. In contrast, diazepam (10 mg/kg, IP) impaired performance of the ANT but not AT animals. These data, supported by results from brain regional autoradiography of [3H]Ro15-4513 and membrane binding of [3H]ZG-63 and [35S]TBPS as influenced by these ligands, strongly suggest that only ligands with full agonist actions on mutant (ANT) but not wild-type (AT) alpha 6-containing GABAA receptors are able to produce motor impairment in the ANT rats.     

Reversal of innate aversions: Attempts to induce a preference for chili peppers in rats.

Although humans frequently develop preferences for innately unpalatable bitter or irritant substances, such preferences are extremely rare in animals. An attempt was made to understand the nature of this difference by 5 experiments with Charles River albino rats, using chili pepper as the unpalatable substance. In parallel with major aspects of the human experience with chili pepper, Ss were exposed to it as a flavoring in all their food for periods up to 11 mo from birth without significant preference enhancement. Gradual introduction of chili into the diet also had no effect, nor did poisoning and safety experiences designed to teach Ss that only chili-flavored foods were safe to eat. Seven pairings of chili-flavored diet with prompt recovery from thiamine deficiency did significantly attenuate the innate aversion and may have induced a chili preference in at least 1 case. Extensive experience with chili did not reliably make Ss much less sensitive to its oral effects. The only reliable way to eliminate chili aversion in rats is to destroy their chemical irritant sense, which was accomplished in 1 group. (29 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of hypnotics on mice genetically selected for sensitivity to ethanol

It was previously shown that the rate of disappearance of blood ethanol was identical for two lines of mice selectively bred for differences in sleep-time after ethanol administration. The ED50 values for the loss of righting response with ethanol were significantly different at 3.64 g per kg for the SS line and 1.65 g per kg for the LS line. In the present study the mean sleep time is 367 sec for SS mice and 9342 sec for LS mice. The ED50 values remain essentially the same as previously reported. Unchanged LD50 values for ethanol, however, are not different at 4.8 g per kg for the SS and 4.5 g per kg for the LS line of mice. The ED50 value for loss for righting response following administration of methanol, butanol and t-butanol is approximately 2 fold greater for the SS line of mice than for the LS line. The ED50 values for sodium pentobarbital or ether in the 2 lines of mice for loss of righting response are virtually identical. In addition, the sleep-time values obtained after the administration of pentobarbital, chloral hydrate, trichloroethanol and paraldehyde are not significantly different. These data indicate that while the SS and LS lines of mice differ in central nervous system sensitivity to ethanol, methanol, butanol and t-butanol it is implied that they do no differ in central nervous system sensitivity to other hypnotic agents tested. Proof of this latter suggestion awaits determination of metabolic rates, and brain levels of these other depressants.     

Sensitivity to low doses of ethanol and pentobarbital in mice selected for sensitivity to hypnotic doses of ethanol.

Assessed sensitivity to low doses of ethanol and pentobarbital in mice that had been selectively bred with respect to ethanol sleep time (the length of time an animal remains on its back following a hypnotic dose of ethanol). The hypothesis investigated was that short-sleep (SS) Ss might be more sensitive than long-sleep (LS) Ss to excitatory effects produced by low doses of depressants. In support of this hypothesis, SS Ss were more active in an open-field test after ethanol than were LS Ss. Two experiments were conducted, using 88 LS and 88 SS Ss. The lines did not differ in performance on a rotating-rod apparatus after these same doses of ethanol, suggesting that the difference in open-field activity was not attributable to a greater impairment of locomotor activity in LS Ss. A similar difference in the open-field activity of the selected lines was observed with pentobarbital. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Electrophysiological responses to ethanol, pentobarbital, and nicotine in mice genetically selected for differential sensitivity to ethanol.

Examined cortical EEG changes induced by ethanol (4.3 and 1.4 g/kg, ip), pentobarbital (50 and 16 mg/kg), and nicotine (1.0 g/kg) in long-sleep (LS) and short-sleep (SS) male mice that were genetically selected for differential sleep times induced by a hypnotic dosage of ethanol. Ethanol (4.3 g/kg) caused EEG changes that paralleled the behavioral differences, whereas no differences between selected lines were observed following the activating dose (1.4 g/kg). Data support the notion that the known difference in ethanol sleep times is due not to greater SS sensitivity to ethanol activation but rather to greater LS sensitivity to ethanol hypnosis. No differences between selected lines were observed following 50 mg/kg pentobarbitol, which again parallels previous behavioral data. SS mice were more responsive to pentobarbital activation (16 mg/kg). Nicotine more severely reduced EEG power and heart rate in LS Ss; a continuous infusion of nicotine elicited a distinct pattern of behavioral stereotypy for each selected line, with more profound motor and reflex depression in LS Ss. The lines do not differ in rate of nicotine metabolism, hence they must differ in CNS sensitivity to nicotine. Thus, mice selectively bred for differential sensitivity to ethanol also differ in electrophysiological and behavioral responses to nicotine. (35 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The influence of transportation stress on selected nutritional parameters to establish the necessary minimum period for adaptation in rat feeding studies

The optimal length of the adaptation period after transportation of rats, to be used in nutritional studies, was investigated in this study. After intracontinental transportation of rats by car and by air to and from the laboratory for a total period of 15 h, measurements were carried out for a period of 3 weeks after transport. Control and transported animals were housed in the same laboratory before and after transportation. During transport the animals had access to food and water. As blood collection could also cause stress, a factorial design was carried out with transport and blood collection as main factors. Transport or blood collection did not cause significant effects on the following parameters: body weight, growth, clinical observation, and blood enzyme activities of LDH and ASAT. Water intake was significantly increased after transport. Food intake did not show consistent effects after transport or blood collection. Unexpectedly, blood corticosterone levels were significantly lower in the transported animals at day 1 after transport. After 3 days these levels were back to normal. Blood glucose, blood free fatty acids and blood urea nitrogen concentrations were incidentally decreased, whereas total cholesterol levels showed an incidental rise in the transported rats. The open-field behaviour test revealed no clear-cut results concerning the effects of transport or blood collection on faeces production, rearing and ambulation. Our results indicate that after intracontinental transport, an adaptation period of 3 days appears to be sufficient for rats to be used in nutritional studies.     

Comparison of environmental quality in the districts of the Czech Republic with mortality pattern and selected health parameters

BACKGROUND: Cancer patients treated with the anticancer drug, paclitaxel (Taxol) often experience mild to severe hypersensitivity reactions. It is not known how these reactions are induced and whether the inducer is paclitaxel or its vehicle (i.e., Cremophor EL in 50% ethanol). Molecules present in Cremophor EL are similar in structure to certain nonionic block copolymers that activate complement proteins (i.e., proteins involved in various immune processes). To explore the role of complement in the observed hypersensitivity reactions, we studied the effects of paclitaxel and Cremophor EL plus ethanol on human complement in vitro. METHODS: Serum specimens from healthy individuals and cancer patients were incubated with paclitaxel or with relevant control compounds (Cremophor EL with ethanol, ethanol only, docetaxel, and cyclosporine), and markers of complement activation (SC5b-9 and Bb) were measured by enzyme-linked immunosorbent assay. Similar incubations were performed in the presence of inhibitors of complement activation (i.e., EGTA/Mg2+ and soluble complement receptor type 1 [sCR1]). RESULTS: Paclitaxel in Cremophor EL plus ethanol caused increased formation of SC5b-9 in serum specimens from 10 of 10 healthy control subjects and from five of 10 cancer patients. Experiments with one or more individual sera indicated the above effect was due to Cremophor EL plus ethanol, that increased formation of Bb also occurred, that the drug-induced rise in SC5b-9 was inhibited by sCR1, and that EGTA/Mg2+ partially inhibited SC5b-9 formation and stimulated Bb formation. IMPLICATION: The role of complement activation in hypersensitivity reactions associated with administration of paclitaxel in Cremophor EL plus ethanol should be studied in vivo.     

Value of selected parameters for monitoring efficacy of specific immunotherapy in allergic disorders

Prevention, pharmacotherapy and specific immunotherapy are used as methods to treat patients with allergic disorders of respiratory system. SIT as a method of controlled supply of allergen, releases immunological mechanisms related to humoral, cellular and effector organic response. Role of those mechanisms and type of changes, taking place can be monitored with given immunological parameters. Most convincing proof of effectiveness of desensitisation, is diminishing of manifestation of clinical symptoms. In patients treated with obvious therapeutical progress, tolerance of increased dose of allergen was noted.     

Quantitative microdialysis of ethanol in rat striatum

We have applied a steady-state theory of microdialysis to characterize the diffusion of ethanol through a microdialysis membrane and through rat striatum. Quantitative characterization required measurement of in vitro and in vivo extraction fractions for ethanol and determination of the clearance of ethanol from brain tissue during steady-state perfusion through a microdialysis probe. Extraction fraction of ethanol was determined in vitro by perfusing a known concentration of ethanol through probes immersed in water at 37 degrees C with stirring. The in vitro extraction fraction yielded a probe permeability value of 0.046 +/- 0.004 cm/min that is comparable with an estimate from published measurements for similar dialysis membranes. The in vivo extraction fraction was determined for probes placed in the striatum. Clearance of ethanol and a brain slice concentration profile of ethanol were determined by measurement of the amount of ethanol remaining in the brain tissue during steady-state perfusion of the probe. Steady state was achieved within 10 min after beginning the ethanol perfusion in vivo, and the extraction fraction was not altered by sedation of the rat with pentobarbital. The tissue concentration profile was symmetrical around the probe track, and ethanol was detected 1 mm from the probe. The experimental clearance rate constant value obtained for ethanol (2.0 +/- 0.3 min(-1)) was higher than that expected for removal solely by loss to the blood. The tissue diffusivity for ethanol, Dt, derived from the experimental measurements was 1.2 +/- 0.2 x 10(-5) cm2/sec. This value is greater than expected for interstitial diffusion, suggesting a substantial contribution by transcellular diffusion of ethanol as well. The predicted tissue concentration profile had a higher peak value and did not extend into the tissue (0.5 mm) as much as the experimental profile (1 mm), although there was reasonable agreement between experiment and theory. Our quantitative characterization of the microdialysis behavior of ethanol in brain provides a framework for interpretation of brain microdialysis experiments using ethanol by supplying, inter alia, a means for estimating the ethanol concentration achieved in the tissue volume being sampled by the probe.     

Sucrose-water preference reversal in the water-deprived rat.

Exposed 4 water-deprived male albino Carworth rats to each of 3 preference conditions. When given a 15-min preference test between a 7.4% sucrose solution and water, Ss ingested 81-91% of their total fluid intake from the sucrose bottle. When given a choice between 1 lick of water and 1 lick of the sucrose solution, Ss consistently preferred water. To determine if this water preference was related to dehydration, Ss were allowed to drink water immediately before the 1-lick preference test. In general, water preference was inversely proportional to amount of pretest drinking. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ethanol preloads increase ethanol preference under concurrent random-ratio schedules in social drinkers.

Ethanol (ETOH) preference was measured following ETOH preload doses in normal social drinkers. 11 Ss participated in a 5-session, double-blind choice study. In Session 1, Ss sampled an ETOH beverage (0.8 g/kg). In Sessions 2–5, they consumed a preload beverage containing placebo or ETOH (0.25 or 0.5 g/kg). One hour later, they responded on 2 concurrent random-ratio (RR) schedules. One schedule was associated with ETOH as the reinforcer and the other with money. When the probability of earning money was low, Ss responded more on the ETOH schedule following both ETOH preloads compared with placebo. Consistent with the increased responding for ETOH, Ss reported increased desire for ETOH. These data demonstrate a priming effect of ETOH preloads in normal social drinkers. They also illustrate the use of concurrent RR schedules to quantify ETOH preference. (PsycINFO Database Record (c) 2010 APA, all rights reserved)