Effects of neonatal handling on play and anxiety in F344 and Lewis rats.

Play is an important part of normal childhood development and seen in many mammals, including rats. To better understand the interplay between genotype and postnatal experiences, the effects of neonatal handling on play were assessed in Lewis (LEW) and Fischer 344 (F344) rats. Handled litters experienced brief periods of separation during the first two postnatal weeks. F344 rats were less likely to direct nape contacts toward an untreated Sprague-Dawley (SD) partner and less likely to rotate to a supine position in response to a nape contact. When compared to rats from control litters, handled LEW, and F344 rats were more likely to respond to nape contacts with complete rotations, suggesting that handling increased playful responsiveness to a comparable extent in both strains. SD rats paired with handled inbred rats had more nape contacts than those paired with non-handled rats. While handled LEW rats also tended to direct more nape contacts to the SD partner than non-handled LEW rats there was no difference between handled and non-handled F344 rats. These results could not be readily explained by handling-induced changes in either maternal care or anxiety. These data suggest that the behavioral consequences of neonatal handling may not depend to a great extent on the genetic platform that these manipulations are acting on. These data also suggest that the ability to maintain the ebb and flow between playful solicitation and playful responsiveness may be compromised in F344 rats and may contribute to the lower levels of play in this strain.

Lewis and Fischer 344 rats as a model for genetic differences in spatial learning and memory: Cocaine effects.

Lewis (LEW) and Fischer 344 (F344) rats are considered a model of genetic vulnerability to drug addiction. We previously showed important differences in spatial learning and memory between them, but in contrast with previous experiments demonstrating cocaine-induced enhanced learning in Morris water maze (MWM) highly demanding tasks, the eight-arm radial maze (RAM) performance was not modified either in LEW or F344 rats after chronic cocaine treatment. In the present work, chronically cocaine-treated LEW and F344 adult rats have been evaluated in learning and memory performance using the Y-maze, two RAM protocols that differ in difficulty, and a reversal protocol that tests cognitive flexibility. After one of the RAM protocols, we quantified dendritic spine density in hippocampal CA1 neurons and compared it to animals treated with cocaine but not submitted to RAM. LEW cocaine treated rats showed a better performance in the Y maze than their saline counterparts, an effect that was not evident in the F344 strain. F344 rats significantly took more time to learn the RAM task and made a greater number of errors than LEW animals in both protocols tested, whereas cocaine treatment induced deleterious effects in learning and memory in the highly difficult protocol. Moreover, hippocampal spine density was cocaine-modulated in LEW animals whereas no effects were found in F344 rats. We propose that differences in addictive-like behavior between LEW and F344 rats could be related to differences in hippocampal learning and memory processes that could be on the basis of individual vulnerability to cocaine addiction.

Selective Nerve Root Transection in the Rat Produces Permanent, Partial Nerve Injury Models with Variable Levels of Functional Deficit.

BACKGROUND: The goal of this study was to develop a partial, nonregenerative nerve injury model in a rat that results in permanently reduced motoneuron numbers and function. This model could serve as a platform for the study of therapeutics, such as a reverse end-to-side nerve transfer (i.e., supercharge). The authors hypothesized that transection of one or more of the L4 to L6 nerve roots supplying the sciatic nerve would cause a permanent reduction in muscle force. METHODS: Rats were randomized into five groups that underwent variations of nerve root transections or sham injury. The L4 to L6 nerve roots were selectively transected and capped to prevent regeneration. Tibial and common peroneal nerves were harvested for quantitative histology and retrograde-labeled to assess the number of motoneurons projecting axons. Muscle force and relative muscle mass were assessed as metrics of postinjury motor function. RESULTS: At 6 months, the number of motoneurons projecting axons and myelinated axon counts were reduced in both the tibial and common peroneal nerves after injury in all groups. Transecting both L4 and L5 or both L4 and L6 reduced motoneuron numbers sufficiently below sham numbers to reduce muscle force and mass in major muscles of the hindlimb innervated by both nerves. Transecting L4 reduced muscle force and mass in common peroneal-innervated muscles, whereas transecting L5 reduced muscle force and mass in tibial-innervated muscles. These findings were stable over time. CONCLUSION: Transection of nerve roots produces stable (time-independent) partial nerve injury models with a selective decrease in motor function.

Across-Species Transfer of Protection by Remote Ischemic Preconditioning With Species-Specific Myocardial Signal Transduction by Reperfusion Injury Salvage Kinase and Survival Activating Factor Enhancement Pathways.

RATIONALE: Reduction of myocardial infarct size by remote ischemic preconditioning (RIPC), that is, cycles of ischemia/reperfusion in an organ remote from the heart before sustained myocardial ischemia/reperfusion, was confirmed in all species so far, including humans. OBJECTIVE: To identify myocardial signal transduction of cardioprotection by RIPC. METHODS AND RESULTS: Anesthetized pigs were subjected to RIPC (4×5/5 minutes hindlimb ischemia/reperfusion) or placebo (PLA) before 60/180 minutes coronary occlusion/reperfusion. Phosphorylation of protein kinase B, extracellular signal-regulated kinase 1/2 (reperfusion injury salvage kinase [RISK] pathway), and signal transducer and activator of transcription 3 (survival activating factor enhancement [SAFE] pathway) in the area at risk was determined by Western blot. Wortmannin/U0126 or AG490 was used for pharmacological RISK or SAFE blockade, respectively. Plasma sampled after RIPC or PLA, respectively, was transferred to isolated bioassay rat hearts subjected to 30/120 minutes global ischemia/reperfusion. RIPC reduced infarct size in pigs to 16±11% versus 43±11% in PLA (% area at risk; mean±SD; P<0.05). RIPC increased the phosphorylation of signal transducer and activator of transcription 3 at early reperfusion, and AG490 abolished the protection, whereas RISK blockade did not. Signal transducer and activator of transcription 5 phosphorylation was decreased at early reperfusion in both RIPC and PLA. In isolated rat hearts, pig plasma taken after RIPC reduced infarct size (25±5% of ventricular mass versus 38±5% in PLA; P<0.05) and activated both RISK and SAFE. RISK or SAFE blockade abrogated this protection. CONCLUSIONS: Cardioprotection by RIPC in pigs causally involves activation of signal transducer and activator of transcription 3 but not of RISK. Protection can be transferred with plasma from pigs to isolated rat hearts where activation of both RISK and SAFE is causally involved. The myocardial signal transduction of RIPC is the same as that of ischemic postconditioning.

Effects of handling and vehicle injections on adrenocorticotropic and corticosterone concentrations in Sprague-Dawley compared with Lewis rats.

The hypothalamic-pituitary-adrenal (HPA) axis is a key factor in the trajectory of the addiction-like cycle (a pattern of behavior characterized by escalating drug use, withdrawal, and relapse) in preclinical and clinical studies. Concentrations of HPA hormones change in laboratory animals in response to standard experimental procedures, including handling and vehicle injections. We compared HPA activity in adult male Lewis (inbred) and Sprague-Dawley (outbred) rats, 2 common strains in rodent models of addiction, after different schedules of handling and saline injections, to explore the extent to which HPA responses differ by strain and whether interindividual differences underlie addiction vulnerability. The 4 treatment conditions were no, short, or long handling and saline injections. In handled groups, rats were handled for 1 to 2 min for 3 times daily and were euthanized after 7 d (short handling) or 14 d (long handling). The injection schedule in the saline injection group mimicked that in a model of binge-like cocaine exposure. Across all treatment groups, concentrations of adrenocorticotropic hormone were higher in Sprague-Dawley than in Lewis rats. In Sprague-Dawley rats, corticosterone concentrations decreased after continued handling but remained constant in Lewis rats. Interindividual variability in hormone levels was greater in Sprague-Dawley than Lewis rats, although corticosterone variability decreased after continued handling. Prolactin did not differ between groups of either Sprague-Dawley and Lewis rats before or after handling. This study underscores the importance of prolonged handling before experimenter-provided drug-administration paradigms and of strain-associated differences that may affect study outcomes.

The differential expression of male sexual behavior in the Lewis, Fischer and Sprague-Dawley rat strains.

Several indices of sexual behavior were characterized for male rats of the Lewis (LEW), Sprague-Dawley (SD) and Fischer (F344) strains. Males were permitted access to a receptive female of their own strain for five 50-min sessions every fifth day. LEW males emitted longer latencies (first mount, intromission, ejaculation and post-ejaculatory interval) and lower frequencies (mounts, intromissions, ejaculations, intromission ratio) relative to F344 males, with the SD strain in general, lying intermediate. Following this assessment, males of each strain were randomly assigned to females of their own or another strain to ascertain whether differences were due to differential female receptivity. Although there were no significant differences during this phase indicative of differential receptivity, the sample size may preclude a definitive interpretation of such results. The data were discussed in the context of other behavioral differences between the strains and the possible neurobiological mechanisms underlying these differences.

Impact of predatory threat on fear extinction in Lewis rats.

Humans with post-traumatic stress disorder (PTSD) are deficient at extinguishing conditioned fear responses. A study of identical twins concluded that this extinction deficit does not predate trauma but develops as a result of trauma. The present study tested whether the Lewis rat model of PTSD reproduces these features of the human syndrome. Lewis rats were subjected to classical auditory fear conditioning before or after exposure to a predatory threat that mimics a type of traumatic stress that leads to PTSD in humans. Exploratory behavior on the elevated plus maze 1 wk after predatory threat exposure was used to distinguish resilient vs. PTSD-like rats. Properties of extinction varied depending on whether fear conditioning and extinction occurred before or after predatory threat. When fear conditioning was carried out after predatory threat, PTSD-like rats showed a marked extinction deficit compared with resilient rats. In contrast, no differences were seen between resilient and PTSD-like rats when fear conditioning and extinction occurred prior to predatory threat. These findings in Lewis rats closely match the results seen in humans with PTSD, thereby suggesting that studies comparing neuronal interactions in resilient vs. at-risk Lewis rats might shed light on the causes and pathophysiology of human PTSD.

Inbred Lewis and Fischer 344 rat strains differ not only in novelty- and amphetamine-induced behaviors, but also in dopamine transporter activity in vivo.

Inbred Lewis (LEW) and Fischer 344 (F344) rats are differentially sensitive to drugs of abuse, making them useful for studying addiction-related neural mechanisms. Here, we investigated whether strain differences in dopamine transporters (DATs) in dorsal striatum (dSTR) and/or nucleus accumbens (NAc) may help to explain their behavioral differences. The behavior of male LEW and F344 rats was assessed in an open-field arena during habituation to novelty and after an i.v. infusion of saline and/or 0.5 mg/kg d-amphetamine (AMPH). In vitro measures of DAT binding, protein and cell-surface expression, as well as in vitro and in vivo measures of function, were used to compare DATs in dSTR and NAc of these two strains. We found that LEW rats exhibited higher novelty- and AMPH-induced locomotion, but F344 rats exhibited greater AMPH-induced rearing and stereotypy. An initial habituation session with i.v. saline minimized the strain differences in AMPH-induced behaviors except that the more frequent AMPH-induced rearing in F344 rats persisted. Strain differences in DAT total protein and basal activity were also observed, with LEW rats having less protein and slower in vivo clearance of locally applied DA in dSTR and NAc. AMPH inhibited in vivo DA clearance in dSTR and NAc of both strains, but to a greater extent in F344 rats. Taken together, the lower basal DAT function in LEW rats is consistent with their greater novelty-induced locomotor activation, whereas the greater inhibition of DA clearance by AMPH in F344 rats is consistent with their marked AMPH-induced rearing behavior.

A comparison of Lewis and Fischer rat strains on autoshaping (sign-tracking), discrimination reversal learning and negative auto-maintenance.

Lewis (LEW) and Fischer (F344) rat strains differ on a number of physiological characteristics, such as hypothalamic-pituitary-adrenal (HPA) axis activity, as well as on behavioral tasks, including those that measure impulsivity and drug reward. Since autoshaping, the phenomenon where animals approach and contact reward-paired conditioned stimuli, has been linked to HPA axis functioning, impulsivity and drug taking, the present study compared LEW and F344 rats on the rate of acquisition and performance of the autoshaping response. Rats were trained on an autoshaping procedure where insertions of one retractable lever (CS(+)) were paired response-independently with food, while insertions of another lever (CS(-)) were not paired with food. LEW rats acquired the autoshaping response more rapidly and also performed the autoshaping response at a higher rate than F344 rats. No differences between the strains were observed when rats were trained on a discrimination reversal where the CS(+) and CS(-) levers were reversed or during a negative auto-maintenance phase where CS(+) lever contacts cancelled food delivery. Potential physiological mechanisms that might mediate the present results, including strain differences in HPA axis and monoamine neurotransmitter activity, are discussed. The finding that LEW (as compared to F344 rats) more readily acquire autoshaping and perform more responses is consistent with research indicating that LEW rats behave more impulsively and more readily self-administer drugs of abuse.

Genetic differences in NMDA and D1 receptor levels, and operant responding for food and morphine in Lewis and Fischer 344 rats.

Previously, we have shown that Lewis (LEW) rats acquire faster than Fischer 344 (F344) rats operant food- and morphine-reinforced tasks under fixed-ratio schedules of reinforcement. The first purpose of the present work has been to study if differences in operant responding behavior may participate in the reported differences in morphine self-administration behavior between both inbred rat strains. To this end, we have analyzed the microstructure of responding obtained under a variable-interval (VI) of food reinforcement by calculating the inter-response time (IRT) for each rat strain. LEW rats exhibited shorter IRTs than F344 rats, suggesting that LEW rats may have an inherent high or compulsive operant responding activity. When subjects of both inbred rat strains were submitted to a schedule of morphine reinforcement of high responding requirements such as progressive ratio schedules, LEW rats also reached significantly higher breaking points and final response ratio than F344 rats for i.v. morphine self-administration. Given that there are neurochemical differences between both rat strains and that glutamatergic N-methyl-D-aspartate (NMDA) and dopaminergic D(1) receptors have been involved in operant responding behavior, a second purpose of this work has been to measure basal NMDA and D(1) receptor levels in these rat strains by quantitative receptor autoradiography. Compared to F344 rats, LEW rats showed higher basal NMDA receptor levels in frontal and cingulate cortex, caudate putamen, central amygdaloid nuclei, and intermediate white layer of superior colliculus, and higher basal D(1) receptor levels in several areas of hippocampus and thalamus, and substantia nigra pars reticulata. Taken together, these results suggest that an inherent high operant responding activity of LEW rats may have a role in the previous reported faster acquisition of opiate-reinforced behavior in operant self-administration paradigms under fixed-ratio schedules of reinforcement. In addition, a basal higher NMDA and D(1) receptor levels of LEW rats compared to F344 rats may participate in the neurochemical background that mediates the behavioral differences between both inbred rat strains.

The effect of nitric oxide inhibition on blood pressure depends on rat strain.

BACKGROUND: Nitric oxide is a continuously released endothelium-derived vasodilator and plays an important role in the maintenance of blood pressure (BP). Rat strains appear to differ in their resting BP and their response to the intravenous administration of N(omega)-nitro-l-arginine methyl ester (l-NAME), a nitric oxide synthase inhibitor. The presence of diabetes and hypertension also leads to differences in BP responses to l-NAME. We postulated that the contribution of NO to resting BP varies between rat strains and certain strains may be more sensitive to the effects of NO blockade. METHODS: Blood pressure was continuously measured using a carotid arterial catheter and the responses to l-NAME were compared in anesthetized Lewis and Sprague-Dawley rats during a 2-h control period and a 2-h experimental period. l-NAME was given by a 50 mg/kg bolus followed by a 10 mg/kg/h infusion via a mesenteric vein. RESULTS: During the control period, the Lewis animals had lower systolic and diastolic BPs of 103 +/- 1 and 80 +/- 1 mm Hg compared with 127 +/- 1 and 105 +/- 1 mm Hg measured in Sprague-Dawley rats (P < 0.01). Although l-NAME infusion increased systolic BP in both strains compared with control values (P < 0.00005), the magnitude was significantly greater in Sprague-Dawley than Lewis animals (P = 0.0142); additionally, the BP was unstable in the Lewis animals. Furthermore, pulse pressure decreased during l-NAME in Lewis animals but increased in Sprague-Dawley animals (P < 0.00005). There were no significant changes in serum concentrations of aspartate transaminase nor of nitrite plus nitrate after l-NAME in either group. CONCLUSION: These results indicate that the effect of l-NAME on systemic BP differs markedly in Sprague-Dawley and Lewis rats, suggesting that the role of nitric oxide in regulation of resting vascular resistance may differ significantly between these rat strains. Rat strain is an important consideration for valid comparisons between studies.

Differences between the Lewis and Sprague-Dawley rats in chronic inflammation induced norepinephrine sensitivity of cutaneous C-fiber nociceptors.

We investigated whether there are any differences between the Lewis and Sprague-Dawley (SD) rats in chronic inflammation-induced norepinephrine (NE) sensitivity of nociceptors. Activities of C-fiber nociceptors innervating rat hairy hindpaw skin were recorded in an in vitro skin-nerve preparation. Sixty-five percent of C-fibers from inflamed Lewis rats were excited by NE (10 microM), against only 38% of C-fibers from inflamed SD rats. The average of the total impulses evoked in response to NE was also significantly higher in Lewis rats. The alpha2-adrenoceptor antagonist CH 38083 (10 microM) and yohimbine (10 microM) consistently blocked the NE-excitation of both strains. These results show that after chronic inflammation, C-fiber nociceptors of Lewis strain rats have a stronger sensitivity to NE, and that alpha2-adrenoceptors are predominately involved in the NE-sensitivity of inflamed rats in both strains.

Microglial activation and neuronal apoptosis in Bornavirus infected neonatal Lewis rats.

Lewis rats neonatally infected with Borna disease virus have a behavioral syndrome characterized by hyperactivity, movement disorders, and abnormal social interactions. Virus is widely distributed in brain; however, neuropathology is focused in dentate gyrus, cerebellum, and neocortex where granule cells, Purkinje cells and pyramidal cells are lost through apoptosis. Although a transient immune response is present, its distribution does not correlate with sites of damage. Neuropathology is instead colocalized with microglial proliferation and expression of MHC class I and class II, ICAM, CD4 and CD8 molecules. Targeted pathogenesis in this system appears to be linked to microglial activation and susceptibility of specific neuronal populations to apoptosis rather than viral tropism or virus-specific immune responses.

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.

A rat T-cell line that mediates autoimmune disease of the inner ear in the Lewis rat.

In various patterns of sensorineural hearing loss including Ménière's disease, which may show improvement in auditory function following immunosuppressive therapy, an isolated autoimmune disease of the inner ear has been postulated. Because of the lack of well-defined diagnostic criteria to identify autoimmune processes within the inner ear and the fact that the human inner ear is one of the few organs of the body not amenable to diagnostic biopsy, there has been great interest in developing animal models that mimic these clinical entities. Previous studies have found evidence that this process might be cell mediated and that the endolymphatic sac functions as an immunodefensive organ for the inner ear. By heterologous immunization of inbred Lewis rats with inner ear tissue, an autoreactive inner-ear-specific T helper cell line was established. After passive transfer of these cells a labyrinthitis was induced in recipient animals. Immunohistochemically, T helper cells were first identified in the cochlea suggesting that this cell type might carry the autoantigenic epitope. Autoantibodies against inner ear tissue were demonstrated in animals with histologically evident labyrinthitis. We conclude that this experimental design can serve as an animal model for cell-mediated autoimmune disease of the inner ear and could be used to explain the etiology of certain types of sensorineural hearing loss such as Ménière's disease. With this approach the identification of the causative autoantigen should be possible and will lead to the development of appropriate clinical tests to diagnose autoimmune diseases of the inner ear in humans.

Enhanced growth response of airway smooth muscle in inbred rats with airway hyperresponsiveness.

The highly inbred Fisher rat strain demonstrates both hyperresponsiveness of the airways to bronchoconstrictors and increased amounts of airway smooth muscle when compared with Lewis rats. We postulated that the excess airway smooth muscle in Fisher was attributable to a greater sensitivity to endogenous mitogenic stimuli with signaling mechanisms common to contractile stimuli. To test this possibility we investigated differences in the growth response of cultured airway smooth muscle cells (SMC) from these two strains. The Fisher SMC demonstrated an enhanced growth response to fetal bovine serum (FBS), as measured both by cell counting and [3H]thymidine incorporation. The difference in growth response was attributable to a more rapid transition in Fisher than Lewis SMC from the G0/G1 phase to the S phase of the cell cycle. When SMC growth was stimulated by either serotonin, endothelin 1, insulin, platelet-derived growth factor (PDGF), or combinations of the above factors, significant interstrain growth response differences were found only with either human PDGF (AB) or a combination of porcine PDGF (BB) and insulin. A polyclonal antibody to PDGF was less inhibitory to Fisher than Lewis SMC following stimulation with FBS. Thus, interstrain growth differences may reflect different responses to PDGF present in FBS, or to other factors which exert an influence during the G0 or G1 phase of the cell cycle.

Male Fischer 344 and Lewis rats display differences in locomotor reactivity, but not in anxiety-related behaviours: relationship with the hippocampal serotonergic system.

Recent studies have shown that arthritis-susceptible Lewis female rats display a marked hypoactivity of the hypothalamo-pituitary-adrenal (HPA) axis and decreased concentrations of hippocampal serotonin receptors (5-HT1A), when compared with arthritis-resistant Fischer 344 female rats. Although previous studies have suggested that these inter-strain differences may extend to several behaviours, the hypothesis that Fischer 344 and Lewis differ in their anxiety and locomotor scores when placed in novel environments has been only scarcely tested. The present study has thus analysed the behaviours of male Fischer 344 and Lewis rats placed successively in activity cages, in an open field (low and high aversive conditions), and in two animal models of anxiety (the elevated plus-maze, the black/white box). Moreover, because the present study was conducted with male rats, we have also checked whether the HPA axis- and 5-HT1A receptor-related differences previously described between female Fischer 344 and Lewis rats extended to males. Under basal conditions: (i) activity of the HPA axis; and (ii) hippocampal 5-HT1A receptor binding and activity of tryptophan hydroxylase (the rate-limiting enzyme in 5-HT biosynthesis) were decreased in Lewis rats, compared with Fischer 344 rats. In addition, the response of the HPA axis to a mild stress (10 min in a novel environment) was lower in Lewis rats than in Fischer 344. When placed in activity cages, Lewis rats displayed a lower locomotor activity, compared with Fischer 344 rats. In the open-field, Lewis rats cross a lower number of inner squares and groomed less than Fischer 344 rats. In the elevated plus-maze and in the black/white box, Fischer 344 and Lewis rats exhibited similar 'anxious' profiles as none of the rats visited the open arms (elevated plus-maze) and the white compartment (black/white box). This study, which extends earlier neurochemical and neuroendocrine findings in females, suggests that both strains display high levels of anxiety but markedly differ in their locomotor activities. Whether the latter strain difference is due to alterations in the HPA axis and/or the central serotonergic systems is an issue that remains to be explored.

Lewis rats of the inbred strain LEW/Han: life expectancy, spectrum and incidence of spontaneous neoplasms.

Although Lewis rats are frequently used in biomedical research, little is known about their life-data and spontaneous pathology. Therefore, it was the aim of this study to determine the life expectancy, spectrum and incidence of spontaneous neoplasms of the inbred rat strain LEW/Han. A total of 629 LEW/Han rats (305 females and 324 males) from a specified pathogen-free breeding colony were kept from weaning up to their natural death under defined environmental conditions. A complete histological examination was performed on all organs and macroscopically altered tissues of all animals which died during the first three years of the study. These were 296 female (98%) and 213 male (66%) rats. The mean lifespan of the females (27.7 +/- 5.1 months) was significantly shorter than that of the males (32.5 +/- 6.6 months). In both sexes, the lifespan was mainly determined by the occurrence of neoplasms. Of the large spectrum of 52 histologically different tumour types, the highest incidences were observed for adenomas of the pituitary gland and adenomas/adenocarcinomas of the adrenal cortex in both sexes, mammary gland tumours and endometrial carcinomas in females, and C-cell adenomas/adenocarcinomas of the thyroid gland and tumours of the haemopoietic system in males. Of these, the high incidences of tumours of the haemopoietic system in males (27.7%) and of endometrial carcinomas in females (45.2%) should be considered as characteristic features of the strain.

Variable susceptibility of Lewis rats to experimental autoimmune encephalomyelitis.

This report is to alert other investigators that Lewis rats, which are widely employed in studies of autoimmune diseases, vary considerably with respect to susceptibility to experimental autoimmune encephalomyelitis (EAE), depending upon commercial source.