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PubMed2005

Evidence of cellular nicotinic receptor desensitization in rats exhibiting nicotine-induced acute tolerance.

RATIONALE: Individuals vary in their susceptibility to nicotine addiction. However, there is little evidence that behavioral sensitivity to nicotine is dependent upon the functional state of nicotinic cholinergic receptors (nAChRs). OBJECTIVE: To determine the relationship between in vivo pharmacological desensitization (in other words, acute tolerance) and brain regional nAChR function. METHODS: Male Sprague-Dawley rats, trained to discriminate nicotine (0.4 mg/kg free base) from saline in a two-lever drug discrimination task, were tested for the development of acute tolerance. Rats were injected with 0.4 mg/kg nicotine, tested for nicotine discrimination for 2 min, then injected with the same dose of nicotine 90 min, 180 min, and 270 min after the first injection and tested for nicotine discrimination after each injection. These subjects were separated into two groups, desensitizers (DZ) and nondesensitizers (NDZ), based upon performance in the repetitive dosing drug discrimination paradigm. The sensitivity of nAChRs in specific brain regions of these two groups was assessed by the use of an 86Rb+ efflux assay using synaptosomes prepared from the frontal cortex, hippocampus, striatum, and "thalamus," which included the midbrain and hypothalamus as well as the thalamus. RESULTS: The nicotine-induced increase in 86Rb+ efflux was significantly greater in NDZ as compared to DZ in the "thalamus." There was no statistically significant difference in the effects of nicotine in the frontal cortex, hippocampus, and striatum of these two groups. A significant correlation was observed between thalamic 86Rb+ efflux and the rate of behavioral desensitization of individual rats. CONCLUSION: These findings are consistent with the concept that the production of acute tolerance by nicotine in vivo correlates directly with its ability to induce nAChR desensitization at the cellular level.

Animals↗
PubMedDate not supplied

Comparison of dextranomer paste and saline dressings for management of decubital ulcers.

In this open-label, parallel-group study, 23 male spinal cord injury patients aged 23 to 73 years (median 54 years) with a total of 30 exudative decubital ulcers were randomly allocated to receive treatment with dextranomer paste (15 ulcers) or conventional saline dressings (15 ulcers). Treatment was applied at least once every 12 hours and continued for a maximum of 15 days, until the ulcer was clean and covered with new granulation tissue and was suitable for skin grafting. The same physician assessed ulcer status (extent of drainage, granulation, erythema, and edema and the presence or absence of necrosis and epithelialization) each time the study nurse changed the dressings. Treatment with dextranomer paste resulted in significantly greater improvement in ulcer drainage compared with saline; 73% versus 13% of the ulcers, respectively, showed > or =25% improvement in drainage from baseline to the end of the study. Both treatments were well tolerated, with no evidence of any local irritation. Dextranomer paste was more effective than saline dressings in the management of decubital ulcers in spinal cord injury patients.

Adult↗
PubMed2003

Cross-tolerance between spinal neostigmine and morphine in the rat.

BACKGROUND: Direct or indirect acting cholinergic muscarinic agonists such as neostigmine, are potent antinociceptives when administered intrathecally (i.t.). This study examines whether spinal neostigmine tolerance and cross-tolerance to spinal morphine occurs. METHODS: Rats (32/group) were implanted with miniosmotic pumps delivering either i.t. saline 1 microl h(-1) (S), morphine 10 nmol microl(-1) h(-1) (M), or neostigmine 3 nmol microl(-1) h(-1) (N). Latencies (infrared thermal withdrawal rear paw) were measured daily for 6 days after which four animals from each group were given one i.t. challenge dose of morphine (m) 0.1, 1, 10, or 100 nmol, or neostigmine (n) 0.3, 3, 10, or 30 nmol. RESULTS: Neostigmine and morphine-infused animals both developed tolerance to spinal neostigmine, but neostigmine-infused animals showed no significant cross-tolerance to spinal morphine; mean ED(50) nmol (CI 95%) dose-response values were Sn 2.6 (1.9-3.5), Mn 15.6 (9.9-24.6)*, Nn 18.7 (11.7-29.8)*, Sm 0.7 (0.4-1.1), Nm 1.2 (0.8-2.0), Mm 152 (50-461)* (*significance vs saline infused control group). CONCLUSION: Thus, unidirectional cross-tolerance from morphine to neostigmine was evident. Previous studies suggest morphine has a cholinergic mechanism of action partially accounting for its antinociceptive effect, which may explain this observed unidirectional cross-tolerance.

Analgesics, Opioid↗
PubMed1982

Salt tolerance in crop plants monitored by chlorophyll fluorescence in vivo.

The potential of measurements of chlorophyll fluorescence in vivo to detect cellular responses to salinity and degrees of salt stress in leaves was investigated for three crop plants. Sugar beet (Beta vulgaris L.) (salt tolerant), sunflower (Helianthus annuus L.) (moderately salt tolerant), and bean (Phaseolus Vulgaris L. cv Canadian Wonder) (salt intolerant) were grown in pots and watered with mineral nutrient solution containing 100 millimolar NaCl. The fast rise in variable chlorophyll fluorescence yield that is correlated with photoreduction of photosystem II acceptors increased in leaves of sugar beet plants treated with salt suggesting stimulation of photosystem II activity relative to photosystem I. In sunflower, this fast rise was depressed by approximately 25% and the subsequent slow rate of quenching of the chlorophyll fluorescence was stimulated. These differences were more marked in the older mature leaves indicating an increasing gradient of salt response down the plant. The salt effect in vivo was reversible since chloroplasts isolated from mature leaves of salt-treated and control sunflower plants gave similar photosystem II activities. Unlike in sugar beet and sunflower, leaves of salt-treated bean progressively lost chlorophyll. The rate of slow quenching of chlorophyll fluorescence decreased indicating development of a partial block after photosystem II and possible initial stimulation of photosystem II activity. With further loss of chlorophyll photosystem II activity declined. It was concluded that measurements of chlorophyll fluorescence in vivo can provide a rapid means of detecting salt stress in leaves, including instances where photosynthesis is reduced in the absence of visible symptoms. The possible application to screening for salt tolerance is discussed.

Journal Article↗
PubMed1997

Glucagon-like peptide-1 can reverse the age-related decline in glucose tolerance in rats.

Wistar rats develop glucose intolerance and have a diminished insulin response to glucose with age. The aim of this study was to investigate if these changes were reversible with glucagon-like peptide-1 (GLP-1), a peptide that we have previously shown could increase insulin mRNA and total insulin content in insulinoma cells. We infused 1.5 pmol/ kg-1.min-1 GLP-1 subcutaneously using ALZET microosmotic pumps into 22-mo-old Wistar rats for 48 h. Rat infused with either GLP-1 or saline were then subjected to an intraperitoneal glucose (1 g/kg body weight) tolerance test, 2 h after removing the pump. 15 min after the intraperitoneal glucose, GLP-1-treated animals had lower plasma glucose levels (9.04+/-0.92 mmol/liter, P < 0.01) than saline-treated animals (11.61+/-0.23 mmol/liter). At 30 min the plasma glucose was still lower in the GLP-1-treated animals (8.61+/-0.39 mmol/liter, P < 0.05) than saline-treated animals (10.36+/-0.43 mmol/liter). This decrease in glucose levels was reflected in the higher insulin levels attained in the GLP-1-treated animals (936+/-163 pmol/liter vs. 395+/-51 pmol/liter, GLP-1 vs. saline, respectively, P < 0.01), detected 15 min after glucose injection. GLP-1 treatment also increased pancreatic insulin, GLUT2, and glucokinase mRNA in the old rats. The effects of GLP-1 were abolished by simultaneous infusion of exendin [9-39], a specific antagonist of GLP-1. GLP-1 is therefore able to reverse some of the known defects that arise in the beta cell of the pancreas of Wistar rats, not only by increasing insulin secretion but also by inducing significant changes at the molecular level.

Aging↗
PubMed2000

Safety of sputum induction in chronic obstructive pulmonary disease.

The aim of the present study was to evaluate the safety of sputum induction in patients with varying severity of chronic obstructive pulmonary disease. The subjects were 28 smokers with baseline forced expiratory volume in one second (FEV1) of (mean and range) 1.8 (0.8-2.9) L that is 53 (28-69)% of the predicted and reversibility of 2.5 (-7.4-9.9)%. Sputum was induced after premedication with 200 microg salbutamol at increasing concentrations (0.9, 3, 4, and 5%) of hypertonic saline nebulized by an ultrasonic nebulizer. The procedure was well tolerated, and none of the patients reported major side-effects. However, the mean change from prebronchodilator FEV1 during induction was -8.5 (-23-11)%, p=0.001, and from postbronchodilator FEV1 -10.7 (-25-5)%, p<0.0001. Three (11%) of the patients had a fall in FEV1 from the prebronchodilator baseline of >20%, and a further 10 (36%) had a fall of 10-20%. Patients with greater reversibility in airway obstruction seemed to get the best benefit from the bronchodilator pretreatment, since there was an inverse relationship between reversibility in FEV1 and fall in FEV1 during induction (r=-0.4, p=0.03). It is concluded that sputum induction by hypertonic saline inhalation can cause meaningful bronchoconstriction in patients with chronic obstructive pulmonary disease, despite pretreatment with an inhaled beta2-agonist. The results highlight the importance of monitoring spirometry during sputum induction to detect bronchoconstriction.

Aerosols↗
PubMed1990

Cachectic effects of recombinant human tumor necrosis factor in rats.

Treatment of rats with either intermittent bolus i.v. injections or continuous i.v. infusions of the same sublethal daily dose of tumor necrosis factor (TNF) results in decreased food intake and decreased nitrogen balance compared to saline-treated control rats. After 4 days of treatment, rats treated with intermittent bolus doses of TNF develop tolerance to the nutritional effects and consume normal amounts of food and have nitrogen balance similar to those of saline treated rats. Rats receiving the continuous infusion of TNF do not. Rats treated with both routes of TNF lose more weight than pair fed rats who eat the same mean amount as the continuous TNF treated group. In addition, 56% of rats receiving continuous infusion TNF die during the 8-day experimental period while rats receiving either intermittent bolus TNF or similar food intake (pair fed) do not. Body composition studies of rats that completed the 8 days of treatment indicate that rats receiving either continuous infusion or intermittent bolus TNF have increased percentages of body water and reduced percentages of body solid compared to saline treated control rats. Rats pair fed to the food intake of continuous TNF treated rats also had increased percentages of body water and reduced percentages of body solid, but changes were significantly less than those observed in continuous TNF infused rats. Continuous TNF infusion reduced total body nitrogen and potassium while pair feeding did not reduce potassium and reduced nitrogen to a lesser degree. Pair feeding and continuous TNF infusion reduced total body fat to a similar extent. Twice a day administration of TNF resulted in lesser changes in carcass water, solid, nitrogen, lipid, and potassium than continuous infusion of the same dose of TNF. The results indicate that continuous infusion of TNF can produce anorexia, weight loss, edema, loss of body protein, lipid and cell mass, and lethality which is markedly ameliorated with bolus doses of TNF. The findings are consistent with the hypothesis that slow continuous secretion of sublethal amounts of TNF may mediate cancer cachexia.

Animals↗
PubMedDate not supplied

Plasma concentrations of nicotine in rats during tolerance and chronic exposure studies.

A convenient GC/MS method for the quantitation of nicotine is described. Brief and rapid tolerance to the hypertensive action of nicotine was observed during acute administration. Rats continuously exposed to (+)- or (-)-nicotine for 6 days showed significant dose-related suppression of water intake and body-weight decreases for the initial 4 days; then water consumption slowly returned to control levels, while body weight increased, but failed to reach control levels. During the withdrawal period, water consumption rose to levels significantly higher than that of the tartaric acid and water controls. Body weight during the withdrawal phase continued to increase but remained below those of control animals. Blood concentration of nicotine during acute tolerance was found to be 64.3 +/- 17.8 ng/ml whereas the saline controls showed levels of 0.67 +/- 0.67 ng/ml. Nicotine levels which were not detectable before the administration of nicotine, were elevated and constant during days 1 and 6 of the infusion period (320 +/- 80 ng/ml of plasma) and fell to below levels of detectability 24 hr after the termination of the infusion.

Animals↗
PubMed2005

Analysis of salt-stress-inducible ESTs isolated by PCR-subtraction in salt-tolerant rice.

To clarify the mechanisms of stress tolerance in rice and to search for rice genes associated with these mechanisms, we analyzed genes induced by a high salinity treatment using the PCR-subtractive hybridization method (PCR-subtraction). Seedlings of the salt-tolerant rice cultivar Dee-geo-woo-gen (DGWG) were either treated with 250 mM NaCl for 5 h or left untreated, and PCR-subtraction was then performed using the untreated (control) plants as a driver and the NaCl-treated plants as a tester. We obtained 384 clones of tester-specific cDNAs as salt-inducible candidates. Northern analysis performed with the cDNA fragments showed that 65 clones had been induced by the NaCl treatment. Sequence analysis and database searching indicated that these clones have homology to proteins functional for detoxification, stress response, and signal transduction in plants. Of these clones, 22% coded for unknown proteins and 12% gave no hits. We selected eight clones from each functional category and analyzed their expression pattern in DGWG. For temporal analysis, seedlings were treated with H(2)O or 250 mM NaCl for 0, 0.5, 1, 2, 5, 10 or 24 h. Different patterns of transcript regulation were found. For the analysis of expression in response to various types of stress and abscisic acid (ABA) treatments, seedlings were treated for 5 h or 10 h with H(2)O, dehydration, cold (4 degrees C), heat (40 degrees C), mannitol, ABA, or wounding. All clones were strongly up-regulated by osmotic stress (dehydration and mannitol) and the ABA treatment.

Abscisic Acid↗
PubMed2005

Tolerance to metals and assessment of energy reserves in the polychaete Nereis diversicolor in clean and contaminated estuaries.

Estuaries are subject to anthropogenic activities. Because the intrasedimentary worm Nereis diversicolor has ecological characteristics and bioindicator abilities, its use was pertinent in investigating the concepts and cost of tolerance to heavy metals (Cd, Cu, Zn). In this context, two approaches were carried out, performing toxicity tests and estimating energy reserves (glycogen and lipids), in populations originating from a contaminated site (Seine estuary) compared with those from a clean site (Authie estuary). Mean lethal times (LT(50)s) of organisms exposed to zinc from the Seine estuary were higher than those from the Authie estuary, but not of organisms exposed to Cd or Cu. The influence of animal weight and salinity on the sensitivity of worms also was studied. The biggest worms were more tolerant to zinc than the smallest ones, and worms survived longer at a reduced salinity (15 per thousand). Concentrations of glycogen and lipids in each sampling season were higher in specimens from the Authie estuary than in worms from the Seine estuary. No influence of salinity on glycogen and lipid levels was observed. Glycogen concentrations were not influenced by the weight of specimens, whereas lipid concentrations were significantly and positively correlated with weight. In conclusion, worms from the Seine estuary exhibited tolerance to Zn, and the depletion of energy reserves observed in this population could be interpreted as a cost of tolerance.

Adaptation, Physiological↗
PubMed2002

Cellular responses to environmental salinity in the halophilic black yeast Hortaea werneckii.

The development of crop plants with increased salt tolerance necessitates the study of naturally salt-tolerant eukaryotic species. We studied the bio-synthesis of glycerol as a compatible solute in the halophilic eukaryotic microorganism, black yeast Hortaea werneckii. A restriction fragment-differential display technique was used to investigate the transcriptome of the organism. Eight differentially expressed genes were identified in response to growth at different salinities. Although the putative functions of their products, P-type ATPase, ubiquinone reductase, aconitase, RNA helicase, Asn-tRNA ligase, isoamyl alcohol oxidase, and phosphatidylinositol-3-kinase, are not intimately related within the cellular machinery, the results presented here are sufficient to propose a model which describes how H. werneckii adapts to extremely high salinities. Some of these mechanisms of adaptation to raised environmental salinity are similar to those in other salt-sensitive species, e.g. glycerol accumulation, there also appear to be novel mechanisms present such as the use of different energy production mechanisms and post-transcriptional regulation of gene expression. Our results have also provided new data on two genes from two other fungal species, the Neurospora crassa B1D1.130 gene and the Aspergillus ustus amdS-A gene.

Adaptation, Physiological↗
PubMed2000

Inflammatory hyperalgesia induced by zymosan in the plantar tissue of the rat: effect of kinin receptor antagonists.

The Randall-Selitto paradigm (maximal tolerated pressure externally applied by a mechanical device) was used to develop a rat model of localized inflammatory hyperalgesia in order to compare the analgesic effects of bradykinin (BK) B1 and B2 receptor antagonists and of a non-steroidal anti-inflammatory drug (NSAID). Intra-plantar injection of zymosan (12.5 mg per paw) induced a considerable inflammation as evidenced from gross and histological evaluation and a mechanical hyperalgesia at 6 h. The contra-lateral paw of zymosan-treated animals or saline vehicle-injected paws did not exhibit a decreased pressure tolerance, relative to pre-injection measurements. Since the B1 receptor may be induced under inflammatory situations, we examined the amount of corresponding mRNA using quantitative RT-PCR. We found a significant increase of B1 receptor mRNA in the zymosan--but not the saline-injected paw at 6 h. Drugs were given subcutaneously 2 h before the 6 h readings to test their analgesic potential. The kinin B1 receptor antagonists [Leu8]des-Arg9-BK (3-30 nmol/kg) and R-715 (100 nmol/kg), the B2 receptor antagonists Hoe 140 (15 nmol/kg) and LF 16.0687 (3 and 10 mg/kg), as well as the NSAID diclofenac sodium (1 and 3 mg/kg) significantly reversed zymosan-induced hyperalgesia. We conclude that zymosan-induced hyperalgesia is a model suitable for the rapid evaluation of analgesic drugs with a peripheral site of action interfering either with kinin receptors or with prostanoid formation. In this regard, results of the present study confirm that blocking kinin B1 receptors is a novel approach for treatment of inflammatory pain.

Analgesics, Non-Narcotic↗
PubMed1999

Ontogeny of rapid tolerance to the hypnotic effects of ethanol.

BACKGROUND: Alcohol use typically begins during adolescence. Little is known regarding the antecedents and impact of this early alcohol use, although age-related changes in the neural systems modulating alcohol sensitivity could contribute to the propensity of adolescents to consume alcohol. We have previously observed a marked ontogenetic decline in acute tolerance to ethanol (EtOH), with preweanling pups exhibiting the most acute tolerance (Silveri and Spear, 1998). The objective of this study was to assess whether rapid tolerance shows a similar ontogenetic profile. METHODS: In Experiment I of the present study, female and male Sprague-Dawley preweanling rats at postnatal day (P) 16 or young adults at P56 were examined. On Day 1, preweanlings were pretreated with saline, 1.5, 3.5, or 5.0 g/kg EtOH and adults were pretreated with saline or 3.5 g/kg EtOH. This was followed by challenge with 3.5 g/kg EtOH and assessment of ethanol-induced sleep time on Day 2. In Experiment II, adolescents at P36 were pretreated with saline, 3.5, or 5.0 g/kg EtOH on Day 1 before Day 2 assessment of sleep time after 3.5 g/kg EtOH. Upon awakening, animals were killed and whole brains removed and analyzed for brain alcohol levels (BrALs). RESULTS: Rapid tolerance was observed in P36 and P56 animals, with EtOH-pretreated animals exhibiting significantly shorter sleep times than age-matched animals treated with saline. In contrast, no evidence for rapid tolerance was seen after any pretreatment dose at P16. Interestingly, although EtOH-pretreated adults woke at higher BrALs than saline-treated adults, this pattern was not evident in the adolescents, which suggests that at this age, metabolic tolerance may play a prominent role in the expression of rapid tolerance. Thus, it seems as though the ability to develop rapid tolerance to EtOH hypnosis emerges during adolescence and continues into adulthood. CONCLUSIONS: Together with previous findings that adolescent animals also display substantial acute tolerance to alcohol (Silveri and Spear, 1998), the propensity of adolescents for developing these two forms of tolerance may have important implications for the increased voluntary consumption of alcohol at this age relative to other ages.

Age Factors↗
PubMed1996

Role of nitric oxide in the development of tolerance and sensitization to behavioural effects of phencyclidine in mice.

1. To determine whether nitric oxide (NO) was involved in tolerance and sensitization to the effects of phencyclidine (PCP), we examined NO synthase activity and the number of NADPH-diaphorase (NADPH-d)-positive cells in discrete brain regions of saline-, acute PCP- and repeated PCP-treated mice. We also investigated the effects of a NO synthase inhibitor, NG-nitro-L- arginine methyl ester (L-NAME), on the behavioural changes induced by repeated PCP treatment in mice. 2. Acute PCP (1, 3, and 10 mg kg-1, s.c.) treatment induced dose-dependent hyperlocomotion, motor incoordination and stereotyped behaviours, consisting of sniffing, head movement and ataxia in mice. 3. In mice treated repeatedly with PCP (1, 3, and 10 mg kg-1 day-1), s.c., once a day for 14 days), the sniffing, head movement, ataxia and motor incoordination induced by PCP were attenuated (indicating the development of tolerance to these behaviours), whereas the hyperlocomotion induced by PCP was potentiated (indicating the development of sensitization to hyperlocomotion). The development of tolerance and sensitization to PCP-induced behaviours in the repeated PCP-treated mice was more marked at the dose of 10 mg kg-1 day-1) than at other doses. 4. NO synthase activity in the cerebral cortex and cerebellum, but not in the striatum and hippocampus, was significantly decreased by acute PCP (10 mg kg-1) treatment in comparison with saline treatment, and such changes in activity in the cerebral cortex and cerebellum were reversed by repeated PCP treatment (10 mg kg-1 day-1). 5. The number of neurones containing NADPH-d reactivity in the cerebral cortex, nucleus accumbens, and striatum of acute and repeated PCP-treated mice showed no change in comparison with saline-treated mice. 6. Tolerance to PCP (10 mg kg-1 day-1)-induced ataxia and motor incoordination was significantly attenuated by combined treatment with L-NAME (50 mg kg-1 day-1 i.p.). 7. Sensitization to PCP-induced hyperlocomotion was further enhanced by combined treatment with L-NAME (50 mg kg-1 day-1). However, NG-nitro-D-arginine methyl ester (D-NAME, 50 mg kg-1 day-1, i.p.), a less active enantiomer of L-NAME, had no effect, suggesting a stereospecific mechanism. 8. The PCP-induced behaviours in animals that had exhibited tolerance and sensitization to PCP (10 mg kg-1 day-1) were not influenced by acute L-NAME (5 and 50 mg kg-1, i.p.) or D-NAME (50 mg kg-1, i.p.) treatment. 9. These results suggest that NO may play an important role in the development, but not in the maintenance, of tolerance and sensitization to the effect of PCP in mice.

Animals↗
PubMed1998

The maximal tolerable intravenous dosage of pentoxifylline in AIDS patients does not inhibit lipopolysaccharide-stimulated tumor necrosis factor alpha production.

Tumor necrosis factor alpha (TNF-alpha) may be involved in the pathogenesis of metabolic and endocrine changes in HIV infection. Pentoxifylline (PTX) is able to suppress the production of TNF-alpha in vitro. The effect of two dosages of intravenously administered PTX on clinical symptoms and ex vivo LPS-stimulated TNF-alpha production was evaluated in six clinically stable AIDS patients in a saline-controlled study. PTX in a dosage of 1.5 mg/min was tolerated without side effects. PTX in a dosage of 2.1 mg/min resulted in intolerable nausea and necessitated termination of infusion after 30 min. The average plasma concentration of PTX after infusion of 1.5 mg/min for 6 hr was 510+/-56 ng/ml, which is considerably below the concentrations that have been reported to suppress TNF-alpha production in vitro. No effect of PTX infusion (1.5 mg/min) on LPS-stimulated TNF production ex vivo was found. Our conclusion is that the maximally tolerated i.v. dosage of PTX in AIDS patients is 1.5 mg/min. LPS-stimulated ex vivo TNF-alpha production, at the LPS concentrations tested, was not inhibited by the plasma concentration of PTX that could be achieved at this dosage.

Acquired Immunodeficiency Syndrome↗
PubMed1987

A new device for continuous ambulatory central venous pressure measurement.

We have developed a device for continuous direct measurement of human central venous pressure (CVP) during space flight. Normal resting CVP is typically in the range of 5-10 mmHg; in zero gravity, the expected changes are +/- 5 mmHg or less. A 1-mm Hg change in CVP can represent a substantial intravascular fluid shift. The device is small, battery powered, and designed to run for at least 24 hr. Pressure is measured in a saline solution-filled catheter inserted into a central vein. The transducer is placed in the axilla at the level of the catheter tip to offset hydrostatic gradients. A pump and an electronic system mount on the leg. This assembly provides a slow, continuous infusion of heparinized saline solution to maintain the patency of the catheter. The electronic system generates a digital display in mm Hg, an analog output, and a visible and audible alarm for excessive pressure. An air-filled syringe allows for a two-point calibration (zero and a positive pressure generated by measured compression of a known gas volume). A two-failure tolerant system minimizes electric shock hazards. Two latex diaphragms separate the saline solution from the transducer surface, and the electronic system and pump chamber are in separate enclosures. A clear polycarbonate case allows bubbles to be seen. The unit has been tested for pump function, temperature stability, drift, and accuracy. We conclude that this approach provides a unit with sufficient stability, accuracy, and temperature insensitivity for measuring ambulatory CVP for up to 28 hr. The design may be suitable for ambulatory measurement of other intravascular and intracardiac pressures.

Catheterization, Central Venous↗
PubMed1984

Acquisition of behaviourally augmented tolerance to ethanol and its relationship to muscarinic receptors.

Two groups of adult male rats were injected daily with ethanol (1.5 g/kg IP in 15% w/v solution) either before (the behaviourally augmented tolerant group) or after (the physiologically tolerant group) being placed in operant chambers. The control groups received daily isotonic saline injections either before or after the operant task. When challenged with ethanol (2.5 g/kg) on day 30 prior to the operant task, the control group was most impaired, while the behaviourally augmented tolerant group was significantly less impaired than the physiologically tolerant group. The two ethanol-treated groups were impaired to the same extent when challenged on day 60. Partial generalization of this behavioural tolerance to ethanol was observed, as the behaviourally augmented tolerant group was less impaired than the physiologically tolerant group for a tail flick response to painful stimuli after an ethanol challenge on day 30. However, the two ethanol-treated groups exhibited similar impairments of locomotor activity after an ethanol challenge on day 40. No differences in muscarinic receptor binding among the control and two ethanol-treated groups were found. These findings demonstrate that behaviourally augmented tolerance to ethanol may be partially generalizable but is unrelated to changes in muscarinic cholinergic receptors.

Animals↗
PubMed1977

Influences of genotype and sex on behavioral tolerance to nicotine in mice.

Spontaneous motor activity in a Y-maze was measured in DBA/2Ibg and C57BL/6Ibg mice which had received nicotine or saline injections three times a day for two, four or seven days. Both genotype and sex influenced the development of tolerance to nocotine's effects on spontaneous motor activity, with DBA males requiring the longest exposure to nicotine and C57 males requiring the shortest drug exposure for tolerance development. DBA and C57 females developed behavioral tolerance equally after two days of pretreatment, but the C57 females showed a greater degree of tolerance after seven days of injections than did the DBA females. The development of behavioral tolerance in DBA males after four days of nicotine pretreatment was associated with the development of behavioral tolerance in DBA males after four days of nicotine pretreatment was associated with the development of drug dispositional tolerance, with minimal evidence for a change in nervous system sensitivity. Drug dispositional tolerance in DBA females, C57 males and C57 females, however, did not seem to affect spontaneous motor activity.

Animals↗