SEARCH · Search PubMed

Results for “sensitization”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 433 records · Page 24Linked to original sources

PubMed1999

Increased acute cocaine sensitivity and decreased cocaine sensitization in GABA(A) receptor beta3 subunit knockout mice.

The role of the GABA(A) receptor beta3 subunit in determining acute cocaine sensitivity and behavioral sensitization to repeated cocaine was measured in mice missing both (-/-), one (+/-), or neither (+/+) allele of the beta3 gene. Locomotor stimulation induced by one cocaine injection (20 mg/kg, i.p.) was found to be greater in -/- mice compared with +/+ mice, whereas cocaine-induced behaviors were intermediate in +/- mice. Amphetamine did not cause greater locomotor responses in -/- mice, suggesting that the increased sensitivity of -/- mice to cocaine does not generalize to other psychomotor stimulants. GABA-stimulated chloride uptake was 51% lower in striatum of -/- mice compared with +/+ mice, but only 27% lower in cortex. After 14 daily cocaine injections, the behavioral response to cocaine was increased in +/+ and +/- mice, but was not increased further in -/- mice. Additionally, repeated cocaine exposure decreased striatal GABA(A) receptor function in +/+ and +/- mice. In -/- mice, GABA(A) receptor function was not decreased any further by repeated cocaine injections. Thus, alterations in the beta3 subunit may be responsible for determining the behavioral responses induced by acute and repeated cocaine treatment, as well as mediating the neurochemical adaptation that occurs during sensitization to repeated cocaine.

Amphetamine↗

PubMed1996

Activation of the ATP-sensitive K+ channel by long chain acyl-CoA. A role in modulation of pancreatic beta-cell glucose sensitivity.

Long-term exposure to elevated levels of long chain free fatty acids decreases glucose-induced insulin secretion from pancreatic islets and clonal pancreatic beta-cells. The mechanism for this loss of glucose sensitivity is at present not known. In this study, we evaluated the possibility that increases in long chain acyl-CoA esters (LC-CoA), the metabolically active form of free fatty acids, might mediate the loss of glucose sensitivity. We observed that cellular levels of LC-CoA increased more than 100% in response to overnight incubation with 0.5 mM palmitic acid complexed to albumin. In the same studies, the total CoA pool increased by about 40%. Patch-clamp studies demonstrated that saturated and unsaturated LC-CoA, but not malonyl-CoA or free CoASH, induced a rapid and slowly reversible opening of ATP-sensitive K+ channels. The effect was concentration-dependent between 10 nM and 1 microM. These findings indicate that the ATP-regulated K/ channels is a sensitive target for LC-CoA and suggest that high levels of LC-CoA, which accumulate in response to hyperglycemia or prolonged exposure to free fatty acids, may prevent channel closure and contribute to the development of beta-cell glucose insensitivity.

Acyl Coenzyme A↗

PubMed1998

The Saccharomyces cerevisiae TSC10/YBR265w gene encoding 3-ketosphinganine reductase is identified in a screen for temperature-sensitive suppressors of the Ca2+-sensitive csg2Delta mutant.

Saccharomyces cerevisiae csg2Delta mutants accumulate the sphingolipid inositolphosphorylceramide, which renders the cells Ca2+-sensitive. Temperature-sensitive mutations that suppress the Ca2+ sensitivity of csg2Delta mutants were isolated and characterized to identify genes that encode sphingolipid synthesis enzymes. These temperature-sensitive csg2Delta suppressors (tsc) fall into 15 complementation groups. The TSC10/YBR265w gene was found to encode 3-ketosphinganine reductase, the enzyme that catalyzes the second step in the synthesis of phytosphingosine, the long chain base found in yeast sphingolipids. 3-Ketosphinganine reductase (Tsc10p) is essential for growth in the absence of exogenous dihydrosphingosine or phytosphingosine. Tsc10p is a member of the short chain dehydrogenase/reductase protein family. The tsc10 mutants accumulate 3-ketosphinganine and microsomal membranes isolated from tsc10 mutants have low 3-ketosphinganine reductase activity. His6-tagged Tsc10p was expressed in Escherichia coli and isolated by nickel-nitrilotriacetic acid column chromatography. The recombinant protein catalyzes the NADPH-dependent reduction of 3-ketosphinganine. These data indicate that Tsc10p is necessary and sufficient for catalyzing the NADPH-dependent reduction of 3-ketosphinganine to dihydrosphingosine.

Acetyl Coenzyme A↗

PubMed1985

A comparison of the pyrimethamine and cycloguanil sensitivities of the pre-erythrocytic and erythrocytic stages of drug-sensitive and -resistant strains of Plasmodium yoelii.

The cycloguanil and pyrimethamine sensitivities of the pre-erythrocytic and erythrocytic stages of a drug-sensitive and drug-resistant strain of Plasmodium yoelii have been compared. With both compounds, and in both parasite strains, the pre-erythrocytic stages were more sensitive to inhibition than were the erythrocytic stages. In the resistant strain the increase in the level of drug tolerance in the erythrocytic stages was paralleled by a corresponding loss of sensitivity in the pre-erythrocytic stages.

Animals↗

PubMed2006

Plasma semicarbazide-sensitive amine oxidase is moderately decreased by pronounced exogenous hyperinsulinemia but is not associated with insulin sensitivity and body fat.

OBJECTIVE: Semicarbazide-sensitive amine oxidase (SSAO) is widely expressed in adipose tissue, where it may contribute to stimulation of glucose transport via GLUT4 recruitment. We tested the relationships of soluble SSAO, as reflected by its plasma activity, with insulin sensitivity and indices of body fat, and determined whether insulin is involved in regulating plasma SSAO activity. MATERIAL AND METHODS: In 24 non-diabetic subjects, the relationships of plasma SSAO activity with insulin sensitivity (M-value and free fatty acid (FFA) suppression during a 3-h hyperinsulinemic (8.3 microU kg-1 s-1), euglycemic clamp), body mass index (BMI 25.5 +/- 3.1 kg m-2), waist-hip ratio and fat mass were assessed. In 16 subjects, the effect of insulin infusion, administered at a rate of 8.3 microU kg-1 s-1 during 3 h, followed by 3-h insulin infusion at a high rate of 41.7 microU kg-1 s-1 on plasma SSAO activity was determined. In the other 8 subjects, the response of plasma SSAO activity to 24-h insulin infused at 8.3 microU kg-1 s-1 was assessed. RESULTS: There were no relationships (all p > 0.10) of plasma SSAO activity (215 +/- 60 mU L-1) with the M-value or with any indices of body fat and FFA before and after insulin suppression. Plasma SSAO activity changed by -7.2 (95% CI, -14.5 to +0.2)% after 3 h (NS) and decreased by 10.1 (95% CI, 19.2 to 1)% after 6 h of insulin infusion (p < 0.05). Plasma SSAO activity did not significantly change after 8 h (change 0.4 (95% CI, -15.3 to +16.2)%, NS) and after 24 h (change -8.8 (95% CI, -27.4 to +9.7)%, NS) of insulin infusion. CONCLUSIONS: It is unlikely that circulating SSAO is a clinically important marker of insulin sensitivity on glucose and fatty acid metabolism. The reduction in plasma SSAO activity in response to pronounced hyperinsulinemia suggests that insulin is involved in the regulation of the soluble form of this enzyme.

Adipose Tissue↗

PubMed1987

The oxygen sensitivity of a multipoint antimony electrode for tissue pH measurements. A study of the sensitivity for in vivo PO2 variations below 6 kPa.

Monocrystalline micro antimony electrodes in a multipoint arrangement as described by Lund et al. were placed on the skeletal muscle surface of the rabbit. Tissue oxygen levels were measured simultaneously with the MDO (Mehrdraht Dortmund Oberfläche) oxygen electrode. The sensitivity for variations in tissue PO2 (PO2(t)) was evaluated for the antimony metal-metal oxide sensor. The sensitivity (delta E/delta log10 PO2)+/- SE was found to be 21.8 +/- 1.2 mV in the interval between 0.1 kPa and 1 kPa and 53 +/- 5 mV in the interval between 1 kPa and 6 kPa. These results are not consistent with the oxygen sensitivity of monocrystalline antimony described in vitro, but are in agreement with the findings of Nilsson & Edwall. A plausible explanation for the S-shaped oxygen sensitivity curve of antimony at oxygen levels below 10 kPa could be an interaction, at the electrode surface, between the dissolved oxygen and the oxygen bound to haemoglobin. If this is the case, the use of an antimony electrode would make possible the determination of the dissociation of oxyhaemoglobin in tissues.

Animals↗

PubMed1990

Heterogeneous radiation and heat sensitivity in vitro of human melanoma xenograft lines established from different lesions in the same patient. Comparisons with the radiation and heat sensitivity of cells isolated from the donor patient's surgical specimens.

Human melanoma xenograft lines were established in athymic nude mice (BALB/c-nu/nu/BOM) from the primary tumour (OKL-PRI), a s.c. metastasis (OKL-SCM) and a lymph node metastasis (OKL-LNM) in the same patient. The three lines differed in growth rate, melanin content, and radiation and heat sensitivity in vitro. The OKL-PRI line grew more slowly than the OKL-SCM and OKL-LNM lines and was the only line that synthesized significant amounts of melanin. The D0 values were 0.96 +/- 0.07 Gy, 0.87 +/- 0.07 Gy and 1.52 +/- 0.09 Gy (X-rays); 143 +/- 21 min, 109 +/- 12 min and 195 +/- 40 min (heat, 42.5 degrees C); and 21.3 +/- 2.7 min, 15.3 +/- 1.7 min and 26.7 +/- 3.0 min (heat, 44.5 degrees C) for the OKL-PRI, OKL-SCM and OKL-LNM line, respectively. The ranking of the lines in treatment sensitivity was equal for radiation and heat. The radiation and heat sensitivities were similar to those for cells isolated directly from the surgical specimens of the donor patient. The lines were thus established from a single neoplastic disease without artificial cloning in vitro or in vivo, and the cellular radiation and heat sensitivity did not change during the establishment procedure, suggesting that they constitute a relevant experimental model system for studies of clonal tumour heterogeneity in response to radiation and hyperthermia treatments.

Acclimatization↗

PubMed1969

Studies on the sensitization of animals with simple chemical compounds. XI. The fate of labeled picryl chloride and dinitrochlorobenzene after sensitizing injections.

The fate of (14)C-labeled allergens injected intradermally into guinea pigs, namely picryl chloride (PCl*) and 2:4 dinitrochlorobenzene (DNCB*), was followed during the induction period of delayed hypersensitivity. Both chemicals were applied in a single injection into one ear in amounts that approached their minimal sensitizing doses (PCl, 0.25 microg; DNCB, 5.0 microg). Radioactivity in the various tissues was determined by liquid scintillation counting after combustion of tissues to CO(2) and H(2)O. The injected allergens seemed to leave the injection site in three phases. A large proportion of allergen escaped rapidly from the ear, about 50% within 3 hr in the case of PCl, within 15 min for DNCB, the difference probably reflecting their unequal reaction constants. Initially there was a "half-life" escape in 2.5 hr with injected dosage of 0.25 microg PCl and in 18 hr for 5.0 microg DNCB. This escape occurred via the regional veins and not via the lymphatics. Radioactive decomposition products of the allergens were already present in the urine within 3-4 hr. After 6-8 hr, the half-life time of escape lengthened to approximately 28 hr for both allergens used in their respective initial dosages, holding up to 2 days after which there occurred still further slowing; between 2 and 4 days the time was about 43 hr for PCl, much longer (72-88 hr?) for DNCB, apparently reflecting different physicochemical properties of this second fraction. Sensitization seemed to be connected with the portion that was present between 12 hr and 4 days of the induction period. It is not known how far the escape of radioactivity during this period may represent gradual hydrolysis of attached picryl and dinitrophenyl groupings, respectively, to form picric acid and dinitrophenol. Gradual accumulation of the second fraction in the regional lymph nodes could definitely be excluded. It was noted that no hypersensitivity arose and essentially no depot of radioactivity existed between 12 hr and 4 days when DNCB was injected in a dose of 0.25 microg, owing to its ready escape from the ear; but 20 times as much DNCB caused sensitization and provided about the same fixed depot as 0.25 microg of picryl chloride. After delayed hypersensitivity had been established, traces of radioactivity were still measurable at the site. This third fraction, probably representing a different coupling product, escaped at a very low rate and was traceable up through several weeks. No demonstrable radioactivity could be detected in thymus, spleen, and mesenteric nodes when examined at short intervals between (1/2) min and 17 days. In analogy with findings on transplantation "immunity" and with studies reported in the following paper, the induction of delayed hypersensitivity can be explained by encounters between lymphoid cells and the hapten complex which is found present in the local site for 4 days, in agreement with Medawar's concept of peripheral sensitization.

Allergens↗

PubMed1974

A new sensitive assay for antibody against cell surface antigens based on inhibition of cell-dependent antibody-mediated cytotoxicity. I. Specificity and sensitivity.

Inhibition of cell-dependent antibody-mediated cytotoxicity has been investigated as a new assay for antibody against cell surface antigens. The cytotoxicity system consisted of effector cells (normal mouse spleen cells), target cells ((61)Cr-labeled chicken erythrocytes), and antitarget cell antibody. Addition of antibody against cell surface antigens in the effector cell population regularly inhibited the cytotoxicity measured in this system. This cytotoxicity inhibition assay (CIA) detected antibody with a variety of specificities: anti-H-2, anti-Thy 1.2, anti-immunoglobulin, and antimouse bone marrow-derived lymphocyte antigen. When the inhibition by anti-H-2 sera was analyzed using effector cells from congenic mice, the activity was found to be directed against specificities mapping in the H-2K, H-2D, and I regions of the H-2 complex, correlating well with the specificities characterized by complement-dependent assays. A comparison between the sensitivity of the CIA and complement-dependent lysis revealed that the CIA was 2-11 times more sensitive for anti-H-2 antisera and 20-780 times more sensitive for certain antisera against subpopulations of the spleen cells (i.e., T cells or B cells). The CIA proved to be precise, sensitive, and reliable. It may become a very useful antibody assay in various species including man.

Animals↗

PubMed2006

Combination of methylated-DNA precipitation and methylation-sensitive restriction enzymes (COMPARE-MS) for the rapid, sensitive and quantitative detection of DNA methylation.

Hypermethylation of CpG island (CGI) sequences is a nearly universal somatic genome alteration in cancer. Rapid and sensitive detection of DNA hypermethylation would aid in cancer diagnosis and risk stratification. We present a novel technique, called COMPARE-MS, that can rapidly and quantitatively detect CGI hypermethylation with high sensitivity and specificity in hundreds of samples simultaneously. To quantitate CGI hypermethylation, COMPARE-MS uses real-time PCR of DNA that was first digested by methylation-sensitive restriction enzymes and then precipitated by methyl-binding domain polypeptides immobilized on a magnetic solid matrix. We show that COMPARE-MS could detect five genome equivalents of methylated CGIs in a 1000- to 10,000-fold excess of unmethylated DNA. COMPARE-MS was used to rapidly quantitate hypermethylation at multiple CGIs in >155 prostate tissues, including benign and malignant prostate specimens, and prostate cell lines. This analysis showed that GSTP1, MDR1 and PTGS2 CGI hypermethylation as determined by COMPARE-MS could differentiate between malignant and benign prostate with sensitivities >95% and specificities approaching 100%. This novel technology could significantly improve our ability to detect CGI hypermethylation.

Animals↗

PubMed2003

Sensitivity to ketamine, alone or in combination with ethanol, is altered in mice selectively bred for sensitivity to ethanol's locomotor effects.

BACKGROUND: Sensitivity to erthanol's locomotor activating and reinforcing effects may be influenced by some common neural mechanisms. Mice selectively bred in replicate for increased (FAST-1 and FAST-2) and decreased (SLOW-1 and SLOW-2) sensitivity to ethanol's locomotor stimulant effects are useful for investigating the neural substrates of ethanol's effects. Previous studies have suggested that differences in N-methyl-d-aspartate (NMDA) receptors may underlie differences in ethanol-induced locomotion in these mice. This study examined the responses of FAST and SLOW mice to ketamine, a fast-acting NMDA antagonist. In addition, reverse-selected lines (r-FAST-1, r-FAST-2, r-SLOW-1, and r-SLOW-2) were tested as a means of verifying correlations detected in the forward-selected lines. Two initial studies characterized ketamine-induced locomotion in DBA/2J (D2) mice, an inbred strain chosen for its high sensitivity to ethanol-induced locomotion. METHODS: After a 2- to 3-day period of habituation to test procedures, mice were given intraperitoneal injections of ketamine alone (0, 5, 10, 20, 30, and 60 mg/kg) or in combination with 1 or 2 g/kg ethanol. Locomotor activity was measured for 20 to 30 min in automated activity monitors. RESULTS: When administered alone, ketamine dose-dependently stimulated the locomotor activity of D2 mice and also reduced the amount of ethanol-induced stimulation. Ketamine stimulated locomotion more in FAST mice than in SLOW mice. Reverse selection abolished these differences, because r-FAST and r-SLOW mice did not differ in their responses to ketamine. Ketamine potentiated ethanol's locomotor effects within FAST mice and potentiated ethanol's locomotor depressant effect within one replicate of SLOW mice. CONCLUSIONS: We propose that sensitivities to ethanol- and ketamine-induced locomotion are genetically correlated and that the combined effects of ethanol and ketamine in FAST mice reflect a leftward shift in ethanol's biphasic dose-response curve.

Animals↗

PubMed1977

Sensitization potentials of methyl, ethyl, and n-butly methacrylates and mutual cross-sensitivity in guinea pigs.

Guinea pigs could be strongly sensitized to methyl, ethyl, and n-butyl methacrylates in ethanol or olive oil by the topical route, or in saline by the intradermal route. For elicitation of skin reactons, topical challenge with the compounds in olive oil or intradermal challenge with saline as the solvent was neccessary. Topical challenge with the methacrylates in ethanol failed to elicit any allergic skin reactions because of their volatility. All sensitized animals responded strongly not only to the inducing methacrylate but also to the other methacrylates, showing that mutual cross-sensitivity had occurred. Since methyl methacrylate has been reported to be a potent sensitizer in humans, the guinea-pig model described here may be useful for screening products before marketing.

Acrylates↗

PubMed1992

Sodium and noradrenaline in cerebrospinal fluid and blood in salt-sensitive and non-salt-sensitive essential hypertension.

1. The effects of dietary sodium on blood pressure and levels of sodium, other electrolytes and noradrenaline (NA) in the cerebrospinal fluid (CSF) and blood of 15 patients with essential hypertension were studied. The CSF and blood sampling was carried out after 7 days of a high salt intake (16-18 g/day) and after 7 days of a low salt intake (1-3 g/day). 2. Blood pressure and sodium concentrations in CSF and serum were significantly higher in the high salt period than the low salt period (CSF Na+ concentration: 147.7 +/- 0.4 mmol/L vs 145.3 +/- 0.5 mmol/L; P less than 0.001). Levels of CSF pressure and potassium or calcium concentrations were not different between the two periods. Plasma NA and plasma renin activity (PRA) were lower and CSF NA levels tended to be lower in the high salt period. 3. The levels and the changes in sodium and NA in CSF were not significantly different between the salt-sensitive (n = 8) and the non-salt-sensitive (n = 7) subjects, but the changes in plasma NA and PRA were smaller in the salt-sensitive subjects. 4. These results indicate that the sympathetic nervous system is less suppressed in salt-sensitive subjects during high salt intake. This may be due to altered neural responsiveness to sodium loading rather than being greater increases in sodium concentration in the central nervous system.

Adult↗

PubMed1991

Characterisation of distinct inositol 1,4,5-trisphosphate-sensitive and caffeine-sensitive calcium stores in digitonin-permeabilised adrenal chromaffin cells.

The effect of inositol 1,4,5-trisphosphate [Ins-(1,4,5)P3] and caffeine on Ca2+ release from digitonin-permeabilised bovine adrenal chromaffin cells was examined by using the Ca2+ indicator fura-2 to monitor [Ca2+]. Permeabilised cells accumulated Ca2+ in the presence of ATP and addition of either Ins(1,4,5)P3 or caffeine released 17% or 40-50%, respectively, of the accumulated Ca2+, indicated by sustained rises in [Ca2+] in the cell suspension. Prior addition of Ins(1,4,5)P3 had no effect on the magnitude of the response to a subsequent addition of caffeine. The response to Ins(1,4,5)P3 was prevented by prior addition of caffeine or CaCl2, indicating that the Ins(1,4,5)P3 response was blocked by elevated [Ca2+]. The responses were essentially identical in the presence of the proton ionophore carbonyl cyanide m-chlorophenylhydrazone, indicating that the Ca2+ release was not from mitochondria or secretory granules and that a proton gradient was not required for Ca2+ accumulation into the Ins(1,4,5)P3- or caffeine-sensitive stores. Ca2+ release from the caffeine-sensitive store was selectively blocked by ryanodine. The Ins(1,4,5)P3-sensitive store was emptied by thapsigargin, which had no effect on caffeine responses. These data suggest that permeabilised chromaffin cells possess two distinct nonoverlapping Ca2+ stores sensitive to either Ins(1,4,5)P3 or caffeine and support previous conclusions that these stores possess different Ca2(+)-ATPases.

Adrenal Glands↗

PubMed1981

Increase of acetylcholine-receptor sensitivity by adenosine triphosphate: a novel action of ATP on ACh-sensitivity.

1. The sensitivity of the nicotinic acetylcholine (ACh)-receptor, measured as the amplitude of ACh-current induced by iontophoretic application of ACh to the frog skeletal muscle endplate, was increased by the action of adenosine triphosphate (ATP). 2. This potentiation was not due to the effect of ATP on ACh-esterase, since the increase of the sensitivity could also be demonstrated by use of carbachol (CCh). 3. Kinetic analysis of the effect of ATP on the dose-response curve of CCh-current suggests that ATP increases the ACh-sensitivity by acting on the allosteric site of receptor-ionic channel complex without changing the affinity of ACh for its recognition site. 4. The equilibrium potential and the life-time of the endplate current (e.p.c.) are not altered by the presence of ATP. 5. These results suggest that ATP increases the ACh-sensitivity by increasing either the conductance of unit channels or the total number of available channels.

Acetylcholine↗

PubMed1988

Initial sensitivity and tolerance to ethanol in mice genetically selected for diazepam sensitivity.

The benzodiazepine (BZ) receptor is coupled with a GABA-receptor chloride-ionophore complex. The BZs augment the GABA-induced increase in chloride conductance, which leads to postsynaptic inhibition. This effect is believed to be responsible for antianxiety, sedative, muscle relaxant, and anticonvulsant effects, but the mechanisms underlying these behavioral effects are poorly understood. Various other sedative-hypnotics, including ethanol and barbiturates, interact with this system, probably contributing to their behavioral effects. We have recently conducted a selective breeding program to develop lines of mice which are diazepam-resistant (DR) and sensitive (DS) (Gallaher EJ, Hollister LE, Gionet SE, Crabbe JC. Psychopharmacology, 93:25-30, 1987); when tested for the duration of rotarod impairment after 20 mg/kg diazepam the DR line was impaired for 71 +/- 13 min compared with 200 +/- 18 min in the DS line. In the current study we tested mice from the DR and DS lines to determine if BZ sensitivity generalized to ethanol. DS mice became ataxic with lower brain ethanol concentrations, and recovered at later times and with lower blood ethanol concentrations, than did DR mice, indicating that sensitivity differences did extend to ethanol. Following a series of sequential doses over 5 to 6 hr DS mice developed minimal rapid tolerance, whereas DR mice developed considerable tolerance. By the end of the day DS mice were therefore much more sensitive to ethanol than were DR mice; this difference was greater in males than in females. High dose ethanol toxicity was studied by assaying brain ethanol concentrations at the cessation of respiration; no differences were found between lines or sexes.

Animals↗

PubMed1989

Sensitivity to ethanol hypnosis and modulation of chloride channels does not cosegregate with pentobarbital sensitivity in HS mice.

Several findings suggest that barbiturates and alcohol produce their sedative effects through a common neural and possibly a common genetic mechanism. We tested this hypothesis by examining the correlation between ethanol and pentobarbital sedative effects in individual animals from a genetically heterogeneous population. The duration of pentobarbital-induced hypnosis (sleep-time) was unrelated to the sleep-time produced by ethanol in heterogeneous stock (HS) mice. Therefore, the present study also examined the effect of ethanol, pentobarbital, and flunitrazepam on muscimol-stimulated chloride flux into brain membranes prepared from HS mice selected for differences in pentobarbital- and ethanol-induced sleep-time. Brain membranes from mice selected for differences in ethanol sleep-time were differentially responsive to ethanol- and flunitrazepam-, but not to pentobarbital-induced augmentation of muscimol-stimulated chloride flux. No differences in augmentation of chloride flux by ethanol, pentobarbital, or flunitrazepam were found in membranes prepared from mice differentially sensitive to pentobarbital hypnosis. The ability of muscimol to stimulate chloride uptake was not related to ethanol or pentobarbital sensitivity. These findings suggest that sensitivity to ethanol is not likely to be genetically linked to pentobarbital sensitivity.

Animals↗

PubMed1995

Chronic ethanol consumption alters effects of ethanol in vitro on brain membrane structure of high alcohol sensitivity and low alcohol sensitivity rats.

In this study, we examined if differences in initial membrane sensitivity to ethanol were associated with development of membrane tolerance to ethanol. High Alcohol Sensitivity (HAS) and Low Alcohol Sensitivity (LAS) rats were administered a 15% ethanol solution in water as the sole source of fluid for 30 days. The amount of ethanol consumed per day did not significantly differ between the HAS and LAS rats. Development of membrane tolerance to in vitro effects of ethanol has been previously reported for bulk membrane fluidity and protein-lipid interaction. Our data expands the understanding of "membrane tolerance" phenomenon to protein distribution and bilayer interdigitation. We also introduce genotype-dependent and genotype-independent properties of the membrane tolerance to ethanol. ethanol treatment produced genotype-dependent and genotype-independent membrane tolerance to ethanol. The in vitro effects of ethanol on synaptic plasma membrane (SPM) protein distribution and lipid bilayer interdigitation were abolished or decreased in the SPM of chronic ethanol-treated HAS rats, as compared with the SPM of HAS control rats (genotype-dependent tolerance). Protein distribution and bilayer interdigitation were not affected by ethanol in vitro in either chronic ethanol-treated or control LAS rats. Genotype-independent tolerance to ethanol in vitro was observed for SPM annular and bulk bilayer fluidity in chronic ethanol-treated HAS and LAS rats. It is concluded that initial sensitivity to ethanol contributes to the development of membrane tolerance to ethanol in HAS and LAS rats.

Alcoholism↗