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Acute Tolerance (acute + tolerance)

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Medical Sciences71%

Selected Abstracts

The Mammalian Circadian Clock Exhibits Acute Tolerance to Ethanol

ALCOHOLISM, Issue 12 2009
Rebecca A. Prosser
Background:, Tolerance to ethanol is observed over a variety of time courses, from minutes to days. Acute tolerance, which develops over 5 to 60 minutes, has been observed for both behavioral and neurophysiological variables and may involve changes in signaling through NMDA, GABA, or other receptors. Previous work has shown that both acute and chronic ethanol treatments modulate photic and nonphotic phase resetting of the mammalian circadian clock located in the suprachiasmatic nucleus (SCN). Although not specifically tested, the data thus far do not point to the development of chronic tolerance to the modulatory effects of ethanol. Here we investigated whether acute tolerance the ethanol occurs with respect to in vitro phase modulation of the SCN clock. Methods:, Mouse brain slices containing the SCN were pretreated with ethanol for varying lengths of time, followed by treatment concurrent with either glutamate or the serotonin agonist, 8-hydroxy-DPAT (DPAT). The phase of the SCN circadian clock was assessed the following day through extracellular recordings of SCN neuronal activity. SCN neuronal activity normally peaks during mid-day, and this rhythm can be shifted by treatment with either glutamate or DPAT. Results:, While concurrent treatment of SCN-containing brain slices with ethanol and glutamate blocks glutamate-induced phase delays of the SCN clock, pretreating the slices with ethanol for ,15 minutes prevents this inhibition. Likewise, while concurrent treatment with ethanol and DPAT enhances DPAT-induced phase advances of the SCN clock, pretreating the slices with ethanol for ,30 minutes prevents this enhancement. Conclusions:, Both the inhibiting and enhancing effects of ethanol on in vitro SCN clock phase resetting show acute tolerance. Additional experiments are needed to determine whether more slowly developing forms of tolerance also occur with respect to the SCN circadian clock. [source]

Effect of a dose of ethanol on acute tolerance and ethanol consumption in alcohol drinker(UChB) and non-drinker (UChA) rats

ADDICTION BIOLOGY, Issue 3 2002
Lutske Tampier
Acute tolerance that develops within minutes of ethanol exposure appears to influence the apparent acute behavioral sensitivity of laboratory animals to ethanol actions. The existence of a correlation between voluntary ethanol consumption and the speed of acquiring acute tolerance has been proposed. In the present paper we investigated the effect of an acute dose of ethanol on tolerance development and on ethanol voluntary consumption in our two selected bred strains, UChA (low ethanol drinker) and UChB (high ethanol drinker) rats. Acute tolerance developed to motor impairment induced by a dose of ethanol of 2.3 g/kg. administered intraperitoneally was evaluated by the tilting plane test. Voluntary ethanol consumption was compared in rats receiving the ethanol dose, to rats receiving a saline intraperitoneal (i.p.) injection. The results show that UChB rats receiving an intoxicating dose of ethanol develop more tolerance and they significantly increased their ethanol consumption compared to the same line that received a saline injection, while no change in acute tolerance and voluntary ethanol consumption were obtained in UChA rats. In conclusion, a possible mechanism by which UChB rats drink high amounts of ethanol appears to be the development of tolerance to the pharmacological effects of ethanol. [source]

The Mammalian Circadian Clock Exhibits Acute Tolerance to Ethanol

ALCOHOLISM, Issue 12 2009
Rebecca A. Prosser
Background:, Tolerance to ethanol is observed over a variety of time courses, from minutes to days. Acute tolerance, which develops over 5 to 60 minutes, has been observed for both behavioral and neurophysiological variables and may involve changes in signaling through NMDA, GABA, or other receptors. Previous work has shown that both acute and chronic ethanol treatments modulate photic and nonphotic phase resetting of the mammalian circadian clock located in the suprachiasmatic nucleus (SCN). Although not specifically tested, the data thus far do not point to the development of chronic tolerance to the modulatory effects of ethanol. Here we investigated whether acute tolerance the ethanol occurs with respect to in vitro phase modulation of the SCN clock. Methods:, Mouse brain slices containing the SCN were pretreated with ethanol for varying lengths of time, followed by treatment concurrent with either glutamate or the serotonin agonist, 8-hydroxy-DPAT (DPAT). The phase of the SCN circadian clock was assessed the following day through extracellular recordings of SCN neuronal activity. SCN neuronal activity normally peaks during mid-day, and this rhythm can be shifted by treatment with either glutamate or DPAT. Results:, While concurrent treatment of SCN-containing brain slices with ethanol and glutamate blocks glutamate-induced phase delays of the SCN clock, pretreating the slices with ethanol for ,15 minutes prevents this inhibition. Likewise, while concurrent treatment with ethanol and DPAT enhances DPAT-induced phase advances of the SCN clock, pretreating the slices with ethanol for ,30 minutes prevents this enhancement. Conclusions:, Both the inhibiting and enhancing effects of ethanol on in vitro SCN clock phase resetting show acute tolerance. Additional experiments are needed to determine whether more slowly developing forms of tolerance also occur with respect to the SCN circadian clock. [source]

Acute, Rapid, and Chronic Tolerance During Ontogeny: Observations When Equating Ethanol Perturbation Across Age

ALCOHOLISM, Issue 9 2001
Marisa M. Silveri
Background: Sensitivity to the motor-impairing and hypnotic effects of ethanol (EtOH) increases notably during development. Less is known, however, about the ontogeny of EtOH tolerance and the ontogenetic relationship among different types of tolerance. Consequently, we compared the ontogenetic development of acute, rapid, and chronic tolerance to EtOH-induced motor impairment and hypothermia in a swim task. Methods: Preweanling, adolescent, and adult female and male Sprague-Dawley rats were given chronic saline (control group), five daily EtOH exposures before EtOH on test day (chronic group), one EtOH exposure before test day (rapid group), or EtOH exposure only on test day (acute groups). Separate groups of animals in the acute groups were tested at 15, 60, or 105 min after injection to estimate acute tolerance development via calculating slopes of the linear regression of impairment relative to brain alcohol levels at each postinjection interval. Initial EtOH perturbation of swim performance was equated across age by varying EtOH dose. Results: Acute tolerance was evident to the motor-impairing effects of EtOH at all ages. When impairment was indexed relative to brain alcohol levels, rapid and chronic tolerance to the motor-impairing effects of EtOH on latency to reach the start was seen across age, although this tolerance tended to be more pronounced in adults. Somewhat different ontogenetic patterns of tolerance development were observed with EtOH-induced hypothermia, a dependent measure for which EtOH perturbation was not equated across age. Conclusions: The degree of initial perturbation by EtOH seems to be an important predictor of tolerance expression during ontogeny. That is, ontogenetic profiles of tolerance development differ significantly when EtOH-induced motor impairment is equated across age rather than dose of EtOH administered . The role of target response measures and context stress should also be considered when exploring ontogenetic expression of EtOH tolerance. [source]

The Genetics of Acute Functional Tolerance and Initial Sensitivity to Ethanol for an Ataxia Test in the LSxSS RI Strains

ALCOHOLISM, Issue 5 2000
Vaughn M. Gehle
Background: It has been proposed that development of tolerance to the behavioral effects of ethanol depends on the degree of impairment produced by the drug; that is, more sensitive individuals should develop greater tolerance. Tests of this hypothesis with respect to acute functional tolerance have produced contradictory results. We tested the hypothesis by examining the genetic relationship between initial sensitivity and acute functional tolerance in the LSXSS recombinant inbred mice. Methods: We tested mice for initial sensitivity to the ataxic effects of 1.75 g/kg of ethanol in a stationary dowel balance test by determining blood and brain ethanol concentrations at fall. Acute tolerance to the ataxic effects of ethanol was determined by measuring blood ethanol concentration (BEC) at regain of dowel balance ability after the first injection (BEC1RB) and after a second ethanol injection of 2.0 g/kg (BEC2RB). Acute tolerance was quantified by the difference in ethanol concentration at the two regains of balance (BEC2RB , BEC1RB) or by the difference between the second regain and one of the initial sensitivity measures (BEC2RB , initial sensitivity). Results: Four different measures of initial sensitivity were taken: two that used BEC values and two that used forebrain or hindbrain ethanol concentrations. We calculated acute tolerance values by using each of these initial sensitivity measures plus BEC2RB. No evidence of a genetic relationship between initial sensitivity and acute tolerance was found, which suggests that these are two independent phenomena with respect to stationary dowel balance. Conclusions: Three conclusions can be drawn from this work: (1) Orbital sinus BEC at early time points (<5 min postinjection) may or may not accurately reflect brain EC in mice, dependent on genotype; (2) there is no genetic relationship between initial sensitivity and acute tolerance to stationary dowel ataxia in the LSXSS RIs; and (3) sex-specific factors affect low-dose ethanol responses on the stationary dowel. [source]

Acute tolerance of juvenile Florida pompano, Trachinotus carolinus L., to ammonia and nitrite at various salinities

AQUACULTURE RESEARCH, Issue 9 2006
Charles R Weirich
Abstract The acute tolerance of juvenile Florida pompano Trachinotus carolinus L. (mean weight±SE=8.1±0.5 g) to environmental unionized ammonia-nitrogen (NH3 -N) and nitrite-nitrogen (NO2 -N) at various salinities was determined via a series of static exposure trials. Median-lethal concentrations (LC50 values) of NH3 -N and NO2 -N at 24, 48, and 96 h of exposure were calculated at salinities of 6.3, 12.5 and 25.0 g L,1 at 28 °C (pH=8.23,8.36). Tolerance of pompano to acute NH3 -N exposure was not affected by salinity, with 24, 48 and 96 h LC50 values ranging from 1.05 to 1.12, 1.00 to 1.08 and 0.95 to 1.01 mg NH3 -N L,1 respectively. Regarding NO2 -N, tolerance of pompano to this environmental toxicant was compromised at reduced salinities. Median-lethal concentrations of NO2 -N to pompano at 24, 48 and 96 h of exposure ranged from 67.4 to 220.1, 56.9 to 140.7 and 16.7 to 34.2 mg NO2 -N L,1 respectively. The results of this study indicate that juvenile Florida pompano are relatively sensitive to acute NH3 -N and NO2 -N exposure, and in the case of the latter, especially at lower salinities. [source]

Effect of a dose of ethanol on acute tolerance and ethanol consumption in alcohol drinker(UChB) and non-drinker (UChA) rats

ADDICTION BIOLOGY, Issue 3 2002
Lutske Tampier
Acute tolerance that develops within minutes of ethanol exposure appears to influence the apparent acute behavioral sensitivity of laboratory animals to ethanol actions. The existence of a correlation between voluntary ethanol consumption and the speed of acquiring acute tolerance has been proposed. In the present paper we investigated the effect of an acute dose of ethanol on tolerance development and on ethanol voluntary consumption in our two selected bred strains, UChA (low ethanol drinker) and UChB (high ethanol drinker) rats. Acute tolerance developed to motor impairment induced by a dose of ethanol of 2.3 g/kg. administered intraperitoneally was evaluated by the tilting plane test. Voluntary ethanol consumption was compared in rats receiving the ethanol dose, to rats receiving a saline intraperitoneal (i.p.) injection. The results show that UChB rats receiving an intoxicating dose of ethanol develop more tolerance and they significantly increased their ethanol consumption compared to the same line that received a saline injection, while no change in acute tolerance and voluntary ethanol consumption were obtained in UChA rats. In conclusion, a possible mechanism by which UChB rats drink high amounts of ethanol appears to be the development of tolerance to the pharmacological effects of ethanol. [source]

The Mammalian Circadian Clock Exhibits Acute Tolerance to Ethanol

ALCOHOLISM, Issue 12 2009
Rebecca A. Prosser
Background:, Tolerance to ethanol is observed over a variety of time courses, from minutes to days. Acute tolerance, which develops over 5 to 60 minutes, has been observed for both behavioral and neurophysiological variables and may involve changes in signaling through NMDA, GABA, or other receptors. Previous work has shown that both acute and chronic ethanol treatments modulate photic and nonphotic phase resetting of the mammalian circadian clock located in the suprachiasmatic nucleus (SCN). Although not specifically tested, the data thus far do not point to the development of chronic tolerance to the modulatory effects of ethanol. Here we investigated whether acute tolerance the ethanol occurs with respect to in vitro phase modulation of the SCN clock. Methods:, Mouse brain slices containing the SCN were pretreated with ethanol for varying lengths of time, followed by treatment concurrent with either glutamate or the serotonin agonist, 8-hydroxy-DPAT (DPAT). The phase of the SCN circadian clock was assessed the following day through extracellular recordings of SCN neuronal activity. SCN neuronal activity normally peaks during mid-day, and this rhythm can be shifted by treatment with either glutamate or DPAT. Results:, While concurrent treatment of SCN-containing brain slices with ethanol and glutamate blocks glutamate-induced phase delays of the SCN clock, pretreating the slices with ethanol for ,15 minutes prevents this inhibition. Likewise, while concurrent treatment with ethanol and DPAT enhances DPAT-induced phase advances of the SCN clock, pretreating the slices with ethanol for ,30 minutes prevents this enhancement. Conclusions:, Both the inhibiting and enhancing effects of ethanol on in vitro SCN clock phase resetting show acute tolerance. Additional experiments are needed to determine whether more slowly developing forms of tolerance also occur with respect to the SCN circadian clock. [source]

GABAA -Receptor , Subunit Knockout Mice Have Multiple Defects in Behavioral Responses to Ethanol

ALCOHOLISM, Issue 12 2001
Robert M. Mihalek
Background: The ,-aminobutyric acid type A receptors (GABARs) are involved in mediating some of the behavioral effects of beverage alcohol (ethanol). However, the unique pharmacological and behavioral responses conferred by each of the various receptor subunits are not well understood. Methods: To address the role of the GABAR , subunit in mediating ethanol responses, gene knockout mice that lack this subunit were tested for a variety of ethanol-induced behavioral responses. Results: Our results indicate that, compared with controls, ,-deficient mice (,,/,) have (1) reduced ethanol consumption, (2) attenuated withdrawal from chronic ethanol exposure, and (3) reduced anticonvulsant (seizure-protective) effects of ethanol. These mice demonstrate a normal anxiolytic response to ethanol and a normal hypothermic response to ethanol, and they develop both chronic and acute tolerance. Conclusions: These results further establish the link between GABARs and specific behavioral responses to ethanol and begin to reveal the role of the , subunit in these responses. [source]

The Genetics of Acute Functional Tolerance and Initial Sensitivity to Ethanol for an Ataxia Test in the LSxSS RI Strains

ALCOHOLISM, Issue 5 2000
Vaughn M. Gehle
Background: It has been proposed that development of tolerance to the behavioral effects of ethanol depends on the degree of impairment produced by the drug; that is, more sensitive individuals should develop greater tolerance. Tests of this hypothesis with respect to acute functional tolerance have produced contradictory results. We tested the hypothesis by examining the genetic relationship between initial sensitivity and acute functional tolerance in the LSXSS recombinant inbred mice. Methods: We tested mice for initial sensitivity to the ataxic effects of 1.75 g/kg of ethanol in a stationary dowel balance test by determining blood and brain ethanol concentrations at fall. Acute tolerance to the ataxic effects of ethanol was determined by measuring blood ethanol concentration (BEC) at regain of dowel balance ability after the first injection (BEC1RB) and after a second ethanol injection of 2.0 g/kg (BEC2RB). Acute tolerance was quantified by the difference in ethanol concentration at the two regains of balance (BEC2RB , BEC1RB) or by the difference between the second regain and one of the initial sensitivity measures (BEC2RB , initial sensitivity). Results: Four different measures of initial sensitivity were taken: two that used BEC values and two that used forebrain or hindbrain ethanol concentrations. We calculated acute tolerance values by using each of these initial sensitivity measures plus BEC2RB. No evidence of a genetic relationship between initial sensitivity and acute tolerance was found, which suggests that these are two independent phenomena with respect to stationary dowel balance. Conclusions: Three conclusions can be drawn from this work: (1) Orbital sinus BEC at early time points (<5 min postinjection) may or may not accurately reflect brain EC in mice, dependent on genotype; (2) there is no genetic relationship between initial sensitivity and acute tolerance to stationary dowel ataxia in the LSXSS RIs; and (3) sex-specific factors affect low-dose ethanol responses on the stationary dowel. [source]

Quantification of heparin-induced TFPI release: a maximum release at low heparin dose

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 6 2002
Michiel J. B. Kemme
Aims Heparin releases tissue factor pathway inhibitor (TFPI) from the endothelium and this release may decrease after repeated high dose heparin administration. The primary aim was to investigate and quantify this phenomenon during a short low dose heparin infusion. Also, the effects of heparin on tissue plasminogen activator (t-PA) were studied. Methods Nine healthy, nonsmoking, male volunteers (range 19,23 years) received a continuous heparin infusion (2000 IU) over 40 min. The endothelial TFPI release rate was estimated from the total TFPI concentration profile using a pharmacokinetic model. Results , Mean ,±,s.d. ,total ,and ,free ,TFPI ,increased ,from ,62.9 ± 9.4/8.3 ± 2.1 ng ml,1 at baseline to 237.2 ± 40.9/111.0 ± 19.9 ng ml,1 after 40 min infusion. The relationship between heparin concentration (anti-IIa activity) and TFPI concentration followed a maximum effect model and a clockwise loop (proteresis) was observed. The TFPI release rate rapidly increased to maximum of 200 ± 45 µg min,1 after 17.5 min heparin infusion but did not increase further although heparin concentrations further doubled. In contrast to TFPI, t-PA antigen decreased from 5.6 ± 1.0 at baseline to 4.5 ± 1.0 ng ml,1 at the end of infusion (t = 40 min) (difference of 1.1 ng ml,1 (95% confidence interval; 0.9, 1.3). Conclusions Our application of concentration-effect models and pharmacokinetic principles to these haemostatic variables showed that endothelial TFPI release has a maximum that is already reached at low heparin dose, corresponding with an anti-IIa activity of 0.08 IU ml,1. The relationship between anti-IIa activity and TFPI release rate showed signs of acute tolerance (clockwise loop) indicating exhaustion of endothelial TFPI pools. These findings may be of importance for the heparin dose used in conditions such as unstable angina, in which the favourable effects of heparin have been ascribed to its ability to release TFPI. [source]

Effect Of Uranyl Nitrate-Induced Renal Failure On Morphine Disposition And Antinociceptive Response In Rats

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 1-2 2000
Jacoba T Van Crugten
SUMMARY 1. The aims of the present study were to administer morphine (14.0 ,mol/kg, s.c.) to male Hooded Wistar rats and to determine the effect of uranyl nitrate-induced renal failure on: (i) the antinociceptive effect of morphine; (ii) the pharmacokinetics of morphine and morphine-3-glucuronide (M3G); and (iii) the relationship between antinociceptive effect and the pharmacokinetics of morphine in plasma and brain. 2. Renal failure was induced by a single s.c. injection of uranyl nitrate and kinetic/dynamic studies were performed 10 days after its administration, when creatinine clearance was 17% of the control group. Antinociceptive effect was measured by the tail-flick method at various times up to 2 h post-drug administration. Concentrations of morphine and M3G in plasma and brain and concentrations of creatinine in urine and serum were determined by specific HPLC methods. 3. After morphine administration, the area under the antinociceptive effect,time curve was decreased by 44% in renal failure rats. There were no differences between control and renal failure rats in: (i) plasma morphine concentration,time curves; (ii) brain morphine concentration,time curves; and (iii) plasma M3G concentration,time curves. Morphine-6-glucuronide was not detected in any plasma or brain sample from rats administered morphine and no M3G was detected in brain. 4. For both control and renal failure rats, the relationships between antinociceptive effect and plasma morphine concentration were characterized by counterclockwise hysteresis loops, probably reflecting a delay for the relatively polar morphine to cross the blood,brain barrier. The relationship between antinociceptive effect and brain morphine concentration in control rats revealed no evidence of acute tolerance and was described by a sigmoidal function. In contrast, the relationship in renal failure rats was characterized by clockwise hysteresis, which is consistent with acute tolerance development. [source]