Lewis rat strain

Guitart, Xavier, Dana Bcitner-Johnson, David W. Marby, Therese A. Kosten, and Eric J. Nestler. 1992. "Fischer and Lewis Rat Strains Differ in Basal Levels of Neurofilament Proteins and Their Regulation by Chronic Morphine in the Mesolimbic Dopamine System." Synapse 12 242-53. 

Kosten, Therese A., Mindy J. Miserendino, Sandra Chi, and Eric J. Nestler. 1994. "Fischer and Lewis Rat Strains Show Differential Cocaine Effects in Conditioned Place Preference and Behavioral Sensitization but Not in Locomotor Activity or Conditioned Taste Aversion." Journal of Pharmacology and Experimental Therapeutics 269 137-44. 

Kulikov, A., Aguerre, S., Berton, O., Ramos, A., Mormede, P., and Chaouloff, E., Central serotonergic systems in the spontaneously hypertensive and Lewis rat strains that differ in the elevated plus-maze test of anxiety, /. Pharmacol. Exp. Then, 281, 775, 1997. 

Type III (immune complex related disease) reactions have been demonstrated by the presence of proteinuria and immune complex deposits in the kidneys of the Brown-Norway, Lewis, and PVG/C rat strains. However, susceptibility to the deposition and the subsequent lesions (glomerulamephritis) are often variable and dependent on the strain (Bigazzi, 1985). For example, despite the appearance of clinical signs and proteinuria, after two-months administration of mercuric chloride, detectable levels of circulating antinuclear autoantibodies can no longer be observed in the Brown-Norway strain (Bellon et al., 1982). By contrast, in PVG/C rats administered mercuric chloride, immune complex deposition and antinuclear autoantibodies are present for longer periods of time however, proteinurea is not observed (Weeping et al., 1978). 

My own research group has reported that the brain rewardenhancing property of -tetrahydrocannabinol, the addictive substance in marijuana and hashish, is much more pronounced in Lewis rats than in other strains, as measured both by direct electrical brain stimulation reward and by in-vivo brain microdialysis of synaptic DA overflow in... 

K. Aghajanian, and Eric J. Nestler. 1993. "Lewis and Fischer Rat Strains Display Differences in Biochemical, Electrophysiologica), and Behavioral Parameters Studies in the Nucleus Accumbens and Locus Coeruleus of Drug Naive and Morphine-Treated Animals." Brain Research 611 7-17. 

Suzuki, Tsutomu, Frank R. George, and Richard A. Meisch. 1988. "Differential Establishment and Maintenance of Oral Ethanol Reinforced Behavior in Lewis and Fischer 344 Inbred Rat Strains." Journal of Pharmacology and Experimental Therapeutics 245 164-70. 

Druet et al. 1977 Mirtcheva et al. 1989 Sapin et al. 1984). As indicated in the section on renal effects, Brown-Norway, MAXX, and DZB rat strains showed susceptibility, whereas Lewis, M520, and AO rats did not (Aten et al. 1991 Druet et al. 1978 Michaelson et al. 1985). Among mouse strains, SJL/N mice are susceptible and DBA, C57BL, and Balb/c mice are not (Hultman and Enestrom 1992 Hultman et al. 1992). In a resistant strain, the Balb/c mouse, immune suppression was manifested as decreased natural killer cell activity in mice administered a diet containing 0.5 mg Hg/kg/day as methyl-mercury (Ilback 1991). 

The authors suggest this is analogous to the time course observed in ASD and the development of chronic disorders. Cohen et al. (2006) also evaluated Lewis rats, a rat strain with blunted HPA axis response and high baseline anxiety-like responses. Administration of corticosterone 1 h prior to predator stress dramatically reduced the number of rats showing EBR compared to control (50% versus 8%). 

Strain differences in the activity of tryptophan hydroxylase, the rate-limiting enzyme in serotonin biosynthesis, have been reported in rats22-23 and in mice.24 Chaouloff et al.22 reported that the activity of tryptophan hydroxylase was decreased in Lewis rats compared with Fisher 344 rats. Kulikov et al.23 reported that in vitro central tryptophan hydroxylase activity was higher in the Lewis strain of rats than in spontaneously hypertensive rats. In mice, Knapp and Mandell24 reported that midbrain tryptophan hydroxylase from two behaviorally different mouse strains, C57B1/6J and A/J, had different stabilities and regulatory properties. 

In rats, a decrease in the affinity of in vitro L-tryptophan binding to hepatic nuclei and nuclear envelopes has been reported in Lewis rats compared with Sprague-Dawley rats.29 While the KD values were similar in both rat strains, the Bmax values were significantly less in Lewis rats compared with Sprague-Dawley rats. Lewis rats are known to be quite susceptible to many inflammatory diseases in response to a wide range of stimuli.30... 

Autoimmune-like phenomena in Brown Norway rats induced by mercuiy(II) chloride peak around day 10 after the last of five subcutaneous injections. After 20 days, immune alterations are mostly at control level, and the kidney effects (e.g. proteinuria) are clearly less than on day 10 (Aten et al., 1988). In addition, low-dose pretreatment of Brown Norway rats with mercuiy(II) chloride prevents development of adverse immunity (Szeto et al., 1999), and neonatal injection of mercury(II) chloride in Brown Norway rats renders them tolerant to mercury-induced (but not gold-induced) autoimmune phenomena (Field et al., 2000). These phenomena, transience of autoimmune effects as well as low-dose protection, are shown to be due at least in part to the development of regulatory immune cells. In the case of mercury(II) chloride, these cells have been identified as either IFN-y-producing CD8+CD45RC high regulatory T cells (Pelletier et al., 1990 Mathieson et al., 1991 Szeto et al., 1999 Field et al., 2003) or RT6.2+ T cells (Kosuda et al., 1994). In view of this, it is relevant to note that Lewis rats that produce predominantly CD8+ regulatory T cells ( suppressor T cells) in response to mercury(II) chloride are resistant to mercury-induced autoimmunity and instead display a polyclonal immunosuppressive response (Pelletier et al., 1987). Based on these differences in strain sensitivity, it is clear that susceptibility to mercury-induced autoimmune effects is dependent on MHC class II haplo-type (Aten et al., 1991). 

Chemicals may exacerbate autoimmunity in genetically predisposed animals or in induced animal models (Kammuller et al., 1989a). The rationale behind using autoimmune-prone animal strains for the purpose of studying and predicting the autoim-munogenic potential of chemicals is that, apart from being probably very sensitive for adverse immune effects, exacerbation of disease is considered one of the possibilities by which chemicals may elicit autoimmune phenomena (Pollard et al., 1999). As mentioned also, the Brown Norway rat is a sensitive rat strain for Th2-dependent phenomena, as is the Lewis rat for cyclosporin-induced autoimmunity. 

McKearn (109) elicited antiidiotypic antibodies against antibodies from inbred Lewis rats having activity toward histocompatibility antigens of the BN rat strain. The latter antibodies were purified, then injected into F,(Lewis x BN) (LBN) rats, which produced the antiidiotypic antibody. Of great interest was the observation that when the immunized LBN hosts were challenged with Lewis spleen cells the graft versus host reaction, as evidenced by increase in weight of local lymph nodes, was diminished as compared with nonimmunized controls. Whether this was caused by an interaction of antiidiotypic antibodies with receptors on T cells remains to be established. 

McKeam (109) states that Lewis rats injected with fibrosarcoma cells from strain BN rats develop not only antibodies to the antigen but also, on prolonged immunization, antiidiotypic antibodies to the anti-BN antibodies. 

Black Mice (NZB) and hybrid strains of NZB-mice (UZB/nzw) is not established, it is believed to be of an auto-immune nature comparable to systemic lupus erythematosls In man. This disease is a useful experimental model for sophisticated drug testing. The activity of cyclophosphamide has been reported in this model The induction of acute allergic encephalomyelitis in the Lewis rat provides a system of delayed hypersensitivity especially useful for assessing anti-inflammatory confounds possessing immunosuppressive properties ... 

The effects of Pb on the mixed lymphocyte response (MLR) have been examined in prior studies. McCabe and colleagues [53] and Farrer and colleagues [54] demonstrated that Pb in vitro at very low concentrations (0.1 pM = 2 pg/dL) significantly enhanced the proliferation and expansion of murine alloreactive CD4+ T lymphocytes in the MLR. The expanded T cell population was found to have a high density of CD4 molecules on the cell surface making them phenotypically similar to memory/effector T lymphocytes. In a study using Lewis strain rats, Razani-Boroujerdi and coworkers [55] also found evidence for Pb-induced stimulation of the in vitro MLR. 

Genetically predisposed animals or induced animal models may also be used to study and predict chemical-induced autoimmunity. In induced models, a susceptible animal strain is immunized with a mixture of an adjuvant and an autoantigen isolated from the target organ. Examples are adjuvant arthritis (AA), experimental allergic encephalomyelitis (EAE) and experimental uveitis in the Lewis strain rat. Examples of spontaneous models... 

Metabolism (e.g., CYPs, COX, Myeloperoxidase) Hapten-Carrier formation (e.g., binding with proteins or aminoacids) PLNA (s.c. injection, indication of possibility to induce systemic allergy) (read-out immunological parameters) Susceptible animals mouse (e.g., NZB, NOD) or rat (BN, Lewis) strains. Parameters for example, autoimmune parameters, histopathology... 

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