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At least 19 recordsLinked to original sources
PubMed2000

Differential neuroendocrine responsiveness to morphine in Lewis, Fischer 344, and ACI inbred rats.

Preclinical evidence suggests there is a link between the responsiveness to stress and the propensity to self-administer drugs of abuse. Our previous findings, for example, have shown a significant positive correlation between the locomotor response to novelty and the acquisition of morphine self-administration in Lewis (LEW), Fischer 344 (F344) and ACI inbred rat strains. As an extension of this work, we now report on the neuroendocrine responses (i.e., corticosterone and prolactin secretion) evoked by morphine administration in these same inbred strains. Male LEW, F344, and ACI rats were surgically prepared with indwelling jugular catheters 7 days prior to the study. Following a habituation period, rats were treated with i.p. saline or morphine (1, 5 or 10 mg/kg). Repeated blood samples were withdrawn via the catheters immediately before and at 20, 40, 60 and 120 min after injection. Plasma samples were assayed for hormone levels by radioimmunoassay. No differences in baseline corticosterone levels were found across strains. There was a significant effect of genotype on the corticosterone response to saline injection (i.e., mild stress), with F344 rats exhibiting sustained elevations in corticosterone compared to LEW and ACI rats. Morphine-induced stimulation of corticosterone release differed significantly across strains, and in this case LEW rats displayed a reduced sensitivity to morphine. Similar to the corticosterone results, LEW rats also had blunted prolactin responses to morphine when compared to F344 rats. Our data demonstrate that genotype is an important factor modulating the neuroendocrine sensitivity to morphine. It is noteworthy that LEW rats acquire self-administration more rapidly than F344 or ACI rats, yet LEW rats display reduced corticosterone responses to stress and morphine. Taking into account the particular conditions of this study (high i.p. doses used here vs. low i.v. doses in self-administration studies), our results do not suggest that corticosterone response to stress and morphine is related to vulnerability to intravenous opiate self-administration. The data, however, are consistent with the idea of that genetic factors might influence the sensitivity to the morphine-induced effects of glucocorticoids across these inbred strains.

Animals↗
PubMed1976

Reagin synthesis in inbred rats. II. Genetic control of reaginic antibody synthesis.

Specific reaginic (IgE) and hemagglutinating (IgG) antibodies were quantified after immunization with ovalbumin aluminum hydroxide gel in BN and ACI inbred rats, as well as their F1, F1 X BN backcross, F2, and F3, and F3 progeny. The dissimilarity of these immune responses indicated that reaginic (IgE) antibody synthesis was influenced by polygenic factors, but not sex, and was controlled by loci different from that governing hemagglutinating (IgG) antibody synthesis. In addition, tissue typing of the BN, ACI, F1, and F3 hybrids suggested that reaginic antibody synthesis was not linked to the major rat histocompatibility locus.

Animals↗
PubMed1980

Variable severity of glomerulonephritis in inbred rats infected with Trypanosoma rhodesiense. Correlation with immunoglobulin class-specific antibody responses to trypanosomal antigens and total IgM levels.

Five strains of inbred rats (ACI, BUF, F344, WF and WL) were infected with Trypanosoma rhodesiense and killed at 28 days for renal pathology and serological studies. The BUF strain demonstrated the most consistent and severe glomerulonephritis, accompanied by high titer IgM antibodies to trypanosomes and high total IgM levels. The WL strain demonstrated mild glomerulonephritis but prominent PAS (+) intracytoplasmic inclusions in proximal convoluted tubules, accompanied by low titer IgM antibodies and slightly elevated total IgM levels. All strains had low to medium titer IgG1 and IgGa antibodies to trypanosomes. Serial serologic studies in BUF rats showed peak titers of IgM, IgGa and IgG1 antibodies to trypanosomal antigens at 10 days. Immune complexes as measured by a C1q binding assay were elevated at 10 days, 3 days following the first detectable antibody responses, and remained so through the 30th day.

Animals↗
PubMed1975

Biochemical and enzymatic characterization of thymic and splenic lymphocyte plasma membranes from inbred rats.

Purified splenic and thymic lymphocytes from the ACI and F344 strains of inbred rats were disrupted by controlled hypotonic treatment, and their plasma membranes were prepared by sucrose density gradient centrifugation. The plasma membrane preparations were highly purified as judged by the structural appearance of the smooth membrane vesicles, by the 10- to 15-fold enrichment of 5'-nucleotidase, which cytochemically localized exclusively in the plasma membranes of intact lymphocytes, by the high cholesterol to phospholipid molar ratio (0.7-1.0), and by the very low specific activities of the enzymes associated predominantly with mitochondria, lysosomes, and endoplasmic reticulum. The protein and the lipid contents of the membranes were 48-55 and 37-48%, respectively. The total lipid content of plasma membranes was characteristically higher in thymic than splenic lymphocytes from both ACI and F344 strains. The specific activity of 5'-nucleotidase was similar in splenic lymphocyte membranes of the ACI strain, and in both the thymic and splenic lymphocyte membranes of the F344 strain. In contrast, the thymic lymphocyte membranes in the ACI strain showed half as much 5'-nucleotidase specific activity. Cytochemical results indicated that the 5'-nucleotidase is located on the outside surface of the lymphocyte plasma membranes.

Adenosine Monophosphate↗
PubMed1985

Co-carcinogenic effects of several Korean foods on gastric cancer induced by N-methyl-N'-nitro-N-nitrosoguanidine in rats.

In study I, 48 ACI and Fisher inbred rats were given MNNG 100 micrograms/ml, with or without 1 per cent or 3 per cent red pepper diet; in study II, 164 Sprague-Dawley rats given MNNG 100 micrograms/ml, with or without 5 per cent or 10 per cent NaCl; in study III, 181 Wistar rats given MNNG 83 micrograms/ml with or without maejoo 10 gm per cent/diet; in study IV, 78 Wistar rats given MNNG 83 micrograms/ml with or without ginseng extract 150 micrograms/ml; in study V, 120 Wistar rats given MNNG 83 micrograms/ml with or without retinyl palmitate 150,000 IU/kg. Except for study II (28 weeks), all rats were fed the diets for 37 weeks and were examined at 38 weeks or 40 weeks. In study I, tumor incidence in rats fed a red pepper diet and MNNG solution were 57 per cent (ACI rats, 1 per cent red pepper) and 63 per cent (Fisher rats, 1 per cent or 3 per cent red pepper) which were higher than control group (44 per cent, 43 per cent); in study II, gastric cancer, 61.9 per cent (10 per cent NaCl-MNNG), 27.3 per cent (control); in study III, gastric cancer, 14.8 per cent (maejoo-MNNG), 24 per cent (control); in study IV, malignant tumor of gastroduodenum, 3.4 per cent (ginseng-MNNG), 32.1 per cent (control); in study V, forestomach papilloma, 10.7 per cent (retinoid-MNNG), 29.4 per cent (control), and cancer in duodenum and small intestine, 50.0 per cent (retinoid-MNNG), 17.6 per cent (control). Thus, gastric carcinogenesis was enhanced by red pepper and a high salt diet, was inhibited by a maejoo and ginseng diet and was not effected by vitamin A.

Animals↗
PubMed2003

Rat strain specific attenuation of estrogen action in the anterior pituitary gland by dietary energy restriction.

The purpose of this study was to compare the effects of a 40% restriction of dietary energy consumption, relative to that consumed by rats allowed to feed ad libitum, on the ability of 17beta-estradiol (E2) to induce pituitary tumorigenesis in two inbred rat strains, ACI and Copenhagen (COP), which are very closely related genetically. Ovary-intact ACI and COP rats were fed either a control or an energy-restricted diet beginning at 8 wk of age. Continuous treatment with E2, released from subcutaneous Silastic tubing implants, was initiated at 9 wk of age and the animals were killed 12 wk later. Estrogen-induced pituitary tumorigenesis is associated with rapid induction of lactotroph hyperplasia, increased pituitary mass, and hyperprolactinemia. E2 significantly increased pituitary mass and circulating prolactin (PRL) in both ACI and COP rats, and this response was significantly greater in ACI rats relative to COP. Dietary energy restriction did not inhibit E2-induced pituitary growth in the ACI rat. By contrast, E2-induced pituitary growth in COP rats was attenuated by dietary energy restriction, as evidenced by quantification of pituitary mass, pituitary weight to body weight ratio, circulating PRL, and pituitary cell proliferation. This study indicates that sensitivity to the inhibitory actions of dietary energy restriction on E2-induced pituitary tumorigenesis is genetically determined.

Animals↗
PubMed1998

Locking and unlocking of running wheel affects circadian period stability differently in three inbred strains of rats.

Running-wheel access has been shown to shorten the circadian period length (tau) of various mammalian species. Due to the close correlation between tau and the level of activity, running wheel-induced changes of the activity level are thought to be responsible for the observed changes in tau. In the present study, the influence of the running wheel on tau and the activity level was examined in three inbred strains of rats (ACI, BH, LEW). Four animals of each strain had free access to their running wheels, while the wheels of the other 4 animals of each strain were mechanically locked. These conditions were changed twice, so that each animal encountered both kinds of changes, that is, from a locked to an unlocked running wheel and vice versa. During the whole study, overall activity was measured by infrared detectors. Running-wheel access resulted in a significant increase of overall activity in strains LEW and ACI. However, significant changes of tau were observed only in LEW rats. These rats showed a significant shortening of tau after the second change of the housing conditions regardless of whether the wheel was locked or unlocked. Consequently, no causal relationship was found between changes of tau and running wheel-induced changes of overall activity. Instead, the results suggest that subtle environmental influences like locking or unlocking the running wheel affect tau in a strain-dependent manner, whereas changes in the activity level are neither necessary nor sufficient to induce changes of tau.

Animals↗
PubMed1982

Cyclophosphamide-induced cardiomyopathy in the rat.

Cyclophosphamide given to ACI inbred rats produced histologic evidence of cardiomyopathy and degenerative vascular changes beginning as early as 4 days after the first of three 150-mg/kg doses (0.9 g/m2). The interval between doses was 14 days to allow bone marrow to recover after each treatment. Twofold increases in heart weight and DNA content were observed 56 days after initial treatment; compensatory hypertrophy and a marked infiltration of the myocardium by lymphocytes were observed histologically at that time. Heart weight and DNA content were again at control levels on Day 126. Hydroxyproline content, which increased along with DNA and weight, did not decrease until after Day 196, confirming a morphologic finding of increased fibrosis after cyclophosphamide which eventually decreased in severity. These data re-emphasize the necessity for considering both the acute and chronic toxic effects, as well as recovery, when developing treatment schedules employing therapeutically effective chemotherapeutic agents.

Animals↗
PubMed1994

[Involvement of ICAM-1/LFA-1 adhesion molecule set in rat orthotopic liver transplantation].

The distribution of ICAM-1/LFA-1-positive cells in rat liver grafts was investigated. The effect on graft survival of graft perfusion with anti-ICAM-1 monoclonal antibody before transplantation was also examined. Using ACI (RT-1av1) and LEW (RT-1(1)) inbred rats, orthotopic liver transplantation was performed both in allogeneic (ACI to LEW) and syngeneic (ACI to ACI) combinations. Transplanted liver tissues on days 2, 4 and 7 were immunohistochemically stained, using mouse anti-rat ICAM-1 monoclonal antibody (1A29, IgG1) and mouse anti-rat LFA-1 monoclonal antibody (WT-1, IgG2a). ACI livers perfused via portal vein with either 1A29, control antibody or lactate-Ringer's solution were transplanted to LEW recipients. ICAM-1 expression in normal ACI livers was confined to the endothelium of large portal vein and some central veins. A weak ICAM-1 expression was also observed on some sinusoidal endothelium. A small number of LFA-1-positive cells were resided in the normal liver. In allografted ACI livers, an intense ICAM-1 expression was induced on sinusoidal endothelium within 2 days after transplantation, and its expression was further increased on days 4 and 7. ICAM-1 expression on hepatocytes was also induced. LFA-1 positive infiltrates were gradually increased in number during the course of rejection, especially in the sinusoidal area. In the syngeneic combination, only a slight ICAM-1 induction on sinusoidal endothelium was observed. ICAM-1 upregulation on target structures of liver graft rejection suggests the importance of ICAM-1/LFA-1 in the pathogenesis of allograft rejection. Liver grafts perfused with anti-ICAM-1 monoclonal antibody were destroyed more rapidly than those perfused with control antibody or lactate-Ringer's solution both in allogeneic and syngeneic combinations. Histological examination revealed spotty ischemic necrosis in grafted liver. Perfusion with the antibody might cause the circulatory disturbance probably through the mechanism differing from alloantigen-specific response.

Animals↗
PubMed1979

Antigenicity of venous allografts.

With isolated exceptions, the clinical use of venous allografts has been disappointing. Considerable evidence indicates that allograft antigenicity plays a major role in the failure of venous allografts when used as arterial replacements. Recent reports suggest that DMSO-cryopreservation of venous allografts may reduce allograft antigenicity while preserving allograft viability. The present study examines the effect of modifications of vein allografts on subsequent allograft antigenicity. Skin grafts were transplanted from ACI to Lewis inbred strains of male rats. Primary skin graft rejection occurred in 9.0 +/- 1.0 days. Subcutaneous implantation of fresh inferior vena cava from ACI rate into Lewis rats resulted in subsequent skin graft rejection in 5.0 +/- 1.0 days, confirming the antigenicity of venous tissue. Cryopreservation of ACI inferior vena cava for seven days prior to implantation, with or without 15% DMSO, resulted in subsequent skin graft rejection in 5.0 +/- 1.0 days. Treatment of ACI inferior vena cava with 0.30% gluteraldehyde for 20 minutes prior to implantation in Lewis rats resulted in skin graft rejection in 9.0 +/- 1.0 days, the same time as a first set rejection. This study indicates that unmodified veins are normally antigenic and that this antigenicity is not eliminated by cryopreservation with or without DMSO. Gluteraldehyde treatment appears to reduce allograft antigenicity, but results in a nonviable graft. At the present time, there is no known way to reduce the antigenicity of viable venous allografts.

Animals↗
PubMed1984

Limb allografts in rats immunosuppressed with cyclosporin A.

The role of cyclosporin A in transplantation of composite tissue for potential reconstructive purposes is examined in the rat hind limb transplant model. Two inbred rat strains were utilized. Brown ACI rat hind limbs were transferred to the dorsum of white Lewis rats with microvascular anastomoses. Twenty transplants were divided into four groups for postoperative immunosuppression: control, no cyclosporin; 7 days of cyclosporin; 21 days of cyclosporin; and continuous cyclosporin from 44-113 days. Hemagglutination and antibody titers were measured. Clinical evaluation and histologic examination at sacrifice were performed and rejection graded. Cyclosporin A has been successful in suppressing rejection in composite allograft transplant across defined major histocompatability barriers. Rats treated with cyclosporin A for a short period of time showed signs of rejection after discontinuation of therapy. Five animals treated continuously on cyclosporin A for up to 113 days showed no sign of rejection clinically, histologically, or immunologically.

Animals↗
PubMed1991

Inbred rat strain comparisons indicate different sites of action for cocaine and amphetamine locomotor stimulant effects.

Cocaine and amphetamine produce several behavioral effects, most notably locomotor stimulation. Biochemically, evidence suggests specific involvement of dopaminergic systems, although not necessarily identical sites, in mediating cocaine- and amphetamine-induced locomotor stimulation. This study examined the effects of cocaine or amphetamine on locomotor activity in rats from the ACI, F344, LEW and NBR inbred strains. Dose-dependent increases in locomotor activity were found for both drugs in all strains. However, large potency and efficacy differences were found. Further, significant strain by drug interactions were found, in that the strain rank order for stimulant response to the two drugs was not identical. Since striatal dopaminergic neurons influence locomotor activity, we also assessed ligand affinity and receptor density of dopamine transporters and dopaminergic D1 and D2 receptors in striatal tissue from these same strains of rats. No differences in these receptor binding parameters were found. These findings support the conclusion that these two drugs produce their locomotor stimulant effects through different sites of action, and that genetic differences in response to these drugs at the behavioral level do not appear to be mediated significantly by differences in structure or number of striatal dopaminergic sites. The further use of genetic methods, however, may aid in determining the specific sites of action of these widely used stimulant drugs.

Amphetamine↗
PubMed1998

Diabetes and dyslipidemia. A new model for transplant coronary artery disease.

BACKGROUND: Clinical observations suggest that transplant coronary artery disease (TxCAD) is immunologically mediated but may be accelerated by metabolic derangements. We developed a rat model of heterotopic heart transplantation in the presence of diabetes and dyslipidemia to further study their role in TxCAD development. METHODS AND RESULTS: Major histocompatibility complex-mismatched strains of inbred rats underwent heterotopic heart transplantation (ACI-to-Lewis allografts). Diabetes (DM) was induced by streptozotocin injection (80 mg/kg) after transplantation; dyslipidemia was worsened by feeding of a 60% high-fructose diet (+F). Allograft transplants were divided into four groups: (1) +DM/+F; (2) +DM/-F; (3) -DM/+F; and (4) -DM/-F. Isograft transplants (Lewis to Lewis, +DM/+/-F) were controls. All animals received daily cyclosporine (5 mg/kg). Grafts surviving > 30 days were evaluated for TxCAD on histological sections and graded 0 to 5 for intimal thickness. All streptozotocin-treated animals were diabetic within 2 weeks, with fourfold increases in plasma glucose concentrations versus nondiabetics. Severe TxCAD was observed in diabetic allografts only. The mean grade of TxCAD in diabetic allografts was 3.2 +/- 0.5 versus 1.1 +/- 0.4 in diabetic isografts (P < 0.03) and zero TxCAD in nondiabetic allografts (P < or = 0.0001). Fructose feeding resulted in a 1.5-fold higher triglyceride and a 1.3-fold higher cholesterol level versus the regular diet (-F) but showed no independent contribution to the development of TxCAD. CONCLUSIONS: These findings suggest that metabolic derangements associated with diabetes play an important role in TxCAD development in heterotopic ACI-to-Lewis rat heart transplantation. In this model of TxCAD in major histocompatibility complex-mismatched, diabetic, and dyslipidemic rats, immunologic and metabolic mechanisms that contribute to TxCAD can be further delineated and approaches to its prevention assessed.

Animals↗
PubMedDate not supplied

Prolongation of rat heart allografts by donor-specific blood transfusion treated with ultraviolet irradiation.

The effect of donor-specific blood transfusion was compared to that of UVB-irradiated donor-specific blood transfusion on heart allograft survival in inbred rats with major histocompatibility differences. In one series ACI rats received heterotopic heart grafts from Lewis rats and 1 mL transfusion of donor-type blood at 1, 2, and 3 weeks prior to the transplantation. Fifty percent of the grafts were permanently accepted (survival greater than 200 days). Following UVB-irradiated donor-specific blood transfusion, 55% of the grafts survived indefinitely. In a mixed lymphocyte reaction ACI lymphocytes are weak responders to Lewis lymphocytes. In another series, Lewis rats received ACI hearts. Donor-specific transfusions at 1, 2, and 3 weeks prior to transplantation did not significantly alter the survival of heart allografts. Lewis lymphocytes react strongly to ACI stimulator cells in a mixed lymphocyte reaction. However, when the donor blood was UVB-irradiated prior to transfusion, the ACI allograft survival was significantly prolonged in this ACI-to-Lewis strain combination. When Lewis rats received W/F hearts following either donor-specific or UVB-irradiated donor-specific transfusions, the hearts' survival was similarly and significantly prolonged, but did not become permanent. Mixed lymphocyte reaction reveals that the stimulation index of Lewis lymphocytes against W/F lymphocytes is greater than that of ACI versus Lewis, but is less than that between Lewis responder cells against ACI stimulators.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1999

Enhanced Ca(2+) mobilization in airway smooth muscle contributes to airway hyperresponsiveness in an inbred strain of rat.

The mechanisms underlying airway hyperresponsiveness are still unknown but increased contractility of airway smooth muscle may play a role. This study sought to demonstrate a relationship between in vivo airway responsiveness and a number of measures of airway smooth muscle responsiveness ex vivo, including intracellular Ca(2+) signaling, by comparing three inbred strains of rat with different degrees of airways responsiveness to methacholine. Lewis, ACI, and Fisher strains of rat were characterized for their pulmonary responses to 5-hydroxytryptamine (5HT) in vivo and Fisher rats were found to be hyperresponsive to 5HT compared with ACI and Lewis rats. The responsiveness of the airways from these strains of rat ex vivo revealed that intraparenchymal airways from Fisher rats significantly narrowed to a greater degree and at a faster rate to 5HT than Lewis rat airways, consistent with their differences in vivo. Intraparenchymal ACI airways, however, narrowed to the same degree as Fisher airways but took longer to do so at a high concentration of 5HT. 5HT caused concentration-dependent increases in intracellular Ca(2+) in airway smooth muscle cells from all three strains of rat, but Fisher and ACI displayed higher responses than Lewis airway smooth muscle. Our results demonstrate that the degree of intracellular Ca(2+) mobilization by 5HT in airway smooth muscle parallels the rate and degree of intraparenchymal airway narrowing and suggest that the degree of intracellular Ca(2+) mobilization plays a role in determining airway smooth muscle contractility.

Airway Resistance↗
PubMed1991

Wheel-running activity rhythms in two inbred strains of laboratory rats under different photoperiods.

Wheel-running activity patterns were studied in two inbred rat strains (ACI/Ztm and LEW/Ztm) under 24-h light-dark cycles with various photoperiods. The ACI strain was characterized by a unimodal activity pattern, whereas the LEW strain exhibited a multimodal activity pattern consisting of two activity bouts about 3-5 h apart. Harmonic spectral analyses and chi square periodograms revealed strain-specific differences in the characteristic rhythmic components of the activity pattern. The ACI strain showed only a strong 24-h rhythm, whereas the LEW strain showed additional rhythmic components with periods of 6, 4.8, and 4 h. Except in very young rats, these strain specific patterns were not affected by an experimental lengthening of the dark period. However, differences between the two strains were found in the free-running period and in the mode of entrainment. Our results indicate that the multimodal activity pattern of the LEW strain is not due to an ultradian bout oscillator, instead it may be the result of a unique coupling of multiple circadian oscillators.

Activity Cycles↗
PubMed1984

Polymorphism of rat alphafetoprotein and albumin genes.

Restriction endonuclease digestion using Hind III and Msp I and Southern blot analysis of DNA from the liver of three inbred rat strains and one outbred strain using cDNA probes yields two banding patterns for the alphafetoprotein and albumin genes. Buffalo and Fischer DNA have one pattern whereas ACI had a different pattern for both genes. Sprague Dawley DNA contains fragments of both patterns suggesting heterozygosity in some individuals of this strain. These polymorphisms do not appear to be associated with any structural or biological differences in the proteins resulting from expression of these genes.

Albumins↗