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Ethanol-paired conditioned stimuli (CSs) are widely thought to invigorate ethanol responding, and thus, precipitate relapse to drinking. However, preclinical studies investigating this issue using Pavlovian-Instrumental-Transfer (PIT) procedures have had mixed results, with some studies finding PIT while others did not. The studies failing to show PIT used Lewis rats and induced ethanol drinking using a post-prandial drinking procedure. The present experiments examined whether either of these two variables influenced the magnitude of PIT observed. In the first experiment, ethanol drinking in Lewis rats was induced using either sucrose fading or post-prandial drinking. In the second experiment, ethanol drinking was induced using post-prandial drinking in either Long-Evans Hooded or Lewis rats. In both experiments, rats were trained to respond for ethanol under a random interval schedule. Subsequently with the lever removed, 2-min light presentations were paired with ethanol deliveries. Finally, with the lever returned, the effect of light presentations on responding was tested while responding was in extinction. Light presentations similarly affected responding in Lewis rats regardless of the method of drinking induction. Likewise, light presentations similarly affected responding in both Lewis and Long-Evans Hooded rats. Neither ethanol induction method nor rat strain affected the magnitude of PIT observed, and thus, neither likely explains previous failures to observe PIT with ethanol-maintained behavior.

The Wistar audiogenic rat (WAR) is an animal model of tonic-clonic epileptic seizures, developed after genetic selection by sister × brother inbreeding of Wistar rats susceptible to sound stimuli. Although metabolic changes have been described in this strain, nothing is known about its mitochondrial metabolism. Here, we addressed mitochondrial aspects of oxidative phosphorylation, oxidative stress, biogenesis, and dynamics in liver, skeletal muscle, and heart of male WARs and correlating them with physiological aspects of body metabolism. The results showed higher mitochondrial content, respiration rates in phosphorylation and noncoupled states, and H2O2 production in WARs. Liver presented higher content of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1α) and mammalian target of rapamycin, proteins related to mitochondrial biogenesis. In agreement, isolated liver mitochondria from WARs showed higher respiration rates in phosphorylation state and ADP-to-O ratio, as well as higher content of proteins related to electron transport chain ATP synthase, TCA cycle, and mitochondrial fusion and fission compared with their Wistar counterparts. Mitochondria with higher area and perimeter and more variable shapes were found in liver and soleus from WARs in addition to lower reduced-to-oxidized glutathione ratio. In vivo, WARs demonstrated lower body mass and energy expenditure but higher food and water intake and amino acid oxidation. When exposed to a running test, WARs reached higher speed and resisted for a longer time and distance than their Wistar controls. In conclusion, the WAR strain has mitochondrial changes in liver, skeletal muscle, and heart that improve its mitochondrial capacity of ATP production, making it an excellent rat model to study PGC1α overexpression and mitochondrial function in different physiological conditions or facing pathological challenges.

The important participation of sympathetic nervous system in various forms of experimental hypertension is well known. This is also true for salt hypertension elicited by excess salt intake in Dahl salt-sensitive rats (for review see Zicha et al. 2012). Two recent studies in Dahl rats (Zicha et al. 2019, Puleo et al. 2020) evaluated the hypothesis on the role of β-adrenergic WNK4-NCC pathway in salt-sensitive hypertension which has been proposed by Mu et al. (2011). Although these studies differed in many experimental details, both of them demonstrated a major importance of α1- rather than β adrenergic mechanisms for the development of salt hypertension in this rat strain. Zicha et al. (2019) demonstrated that chronic β adrenergic blockade by propranolol did not lower blood pressure (BP) in Dahl salt-sensitive rats developing salt hypertension. It also did not modify their sympathetic component or natriuretic response to acute hydrochlorothiazide administration which inhibited the activity of sodium-chloride cotransporter (NCC). Puleo et al. (2020) reported that chronic β-adrenergic blockade failed to affect salt hypertension development or to reduce renal WNK4-NCC pathway. On the other hand, their study demonstrated the important influence of α1 adrenergic pathway on the activity, expression and phosphorylation of NCC. Chronic α1-adrenergic antagonism by terazosin treatment in Dahl salt-sensitive rats, which started before the onset of high salt intake, considerably attenuated the development of salt hypertension. This treatment diminished BP difference between the salt-loaded Dahl salt-sensitive rats and their control groups by 70-75 %. However, terazosin-treated Dahl salt-sensitive animals fed a high-salt diet had not only suppressed renal NCC activity but they also did not respond to acute phenylephrine administration. This suggests that chronic α1-adrenergic blockade affected both renal sodium retention mechanisms and α1-adrenergic vasoconstriction (Puleo et al. 2020). It remains to determine how these two mechanisms contribute to salt hypertension in Dahl rats. We found that the acute ganglionic blockade lowered substantially BP of salt hypertensive Dahl rats, abolishing 45-55 % of the BP difference between salt-loaded Dahl salt-sensitive rats and their control groups (Zicha et al. 2019). If we consider the results of both above studies, it seems that the renal contribution might be responsible for about 25 % of BP elevation seen in Dahl salt-sensitive rats developing salt hypertension, whereas α1-adrenergic vasoconstriction contributes to this BP change by about 50 %. Of course, this consideration is highly speculative. Nevertheless, it might stimulate further effort to distinguish the role of kidney and brain in the pathogenesis of salt hypertension. Perhaps even more promising could be the estimation of renal and extrarenal effects of central sympathoexcitation in Dahl rats (Mark 1991, Gabor and Leenen 2012, Fujita et al. 2009) which is related to central α2-adrenergic mechanisms (Wainford et al. 2015). As far as the role of kidney in the pathogenesis of salt hypertension is concerned (Frame et al. 2019), some attention should also be paid to participation of renal vascular and tubular effects of increased sympathetic tone in these salt hypertensive animals.

Olanzapine can decrease anxiety and impair memory, but there is limited information about length of treatment or sex differences in its effectiveness. Therefore, effects of 21-24 and 41-45 days of treatment and sex differences on anxiety-related behaviour and spatial memory were assessed in PVG/c (PVG/c is the internationally recognised way of referring to this rat strain) male and female rats. From 70 days after birth (PND70), all rats received no drug or 6, 11 or 15 mg/kg/day olanzapine via drinking water. From PND91, they were given four daily tests in an open field, light-dark box, zero maze and Y maze, and then again 21 days later from PND112. At PND91-94, all olanzapine doses decreased open-field ambulation and walking, and 6 and 15 mg/kg/day decreased rearing, increased immobility while 15 mg/kg/day decreased shuttles in the light/dark box (all suggesting higher anxiety). At PND112-115, 11 mg/kg/day increased open-field ambulation, walking, rearing, centre occupancy and light/dark-box shuttles and light-side entries while decreasing open-field immobility and corner occupancy (all suggesting lower anxiety). There were also several results in the open field and light/dark box suggesting olanzapine decreased anxiety for males but increased it for females. A significant olanzapine-related preference for the novel Y-maze arm either improved spatial memory, or decreased anxiety. Olanzapine thus appeared anxiogenic after 21 days' treatment, becoming anxiolytic after 42 days. This could depend on the sex of the rats (females more responsive to lower doses), and the dose (11 mg/kg/day being most effective). Therefore, while olanzapine was generally anxiolytic, it also had some treatment length- and sex-related anxiogenic effects.

Background Inbred strains are characterized by less genetic variation, which suggests usefulness of inbred strains for evaluations of various parameters. In this study, experimental reproducibility in several parameters was compared between an outbred Wistar rat and Wistar King A Hokkaido (WKAH/HkmSlc) rat, the inbred strain that is originated from Wistar rats. Methods Difference of variations was investigated in parameters of body compositions and liver functions such as body weight, liver weight, liver triglycerides (TG), liver cholesterol and plasma alanine aminotransferase activity (ALT) between WKAH rats and outbred Wistar rats by using the coefficient of variation (CV). Results There was no difference in the CVs of body weight and relative liver weight between WKAH and Wistar rats. The CVs of body weight and relative liver weight were below 10% in both WKAH and Wistar rats. The CVs of TG, cholesterol, and ALT in Wistar rats were between 30 and 40%, whereas those in WKAH rats were between 10 and 25%. A low CV level of TG was observed in WKAH rats compared to that in Wistar rats regardless of the duration of the experimental period in those rat strains. Conclusion The low CV values in metabolic parameters involved in liver functions in the inbred rats suggested an advantage of using inbred rather than outbred rats for the evaluation of liver lipid metabolism.

Актуальность. Селектированная на проявление судорог в ответ на сильный звук (аудиогенную эпилепсию, АЭ) линия крыс КрушинскогоМолодкиной (КМ) модель судорожных состояний человека, c быстрым развитием судорожного припадка в ответ на включение звука (100120 дБ). Однако у крыс с АЭ изменений уровня кортикостерона (КС) в крови в связи с судорогами не определяли, хотя анализ связи АЭ и стрессреакции важная практическая задача. Методы. Уровень КС в образцах сыворотки крови определяли с помощью набора у крыс линии КМ, а также у крыс линии 0 , селектированных из гибридной популяции КМ х Вистар на отсутствие АЭ, и у крыс популяции Вистар. Результаты. У всех крыс КМ был зарегистрирован аудиогенный припадок, тогда как у крыс линии 0 и Вистар судорог не было. Через 30 мин после действия звука (и судорог) у крыс КМ повышеается уровень КС, тогда как сразу после судорог (через 13 мин) данная реакция не обнаруживается. У крыс линии 0 обнаружен достоверно более высокий фоновый уровень КС, по сравнению с КМ и Вистар. Уровень КС у них, как и у крыс Вистар, после действия звука не изменялся. Заключение. Подъем уровня КС в крови после действия звука наблюдали только у крыс КМ через 30 мин после припадка АЭ. Крысы линии 0 , у которых нет судорог в ответ на звук, обнаружили более высокий, чем у КМ и Вистар уровень КС в фоне., Aims. The KrushinskyMolodkina (KM) rat strain, which was selected for a seizure response to a sound (audiogenic epilepsy, AE), is known as a model of human seizure states. Although the association of blood CS with stress reaction is an important practical issue, blood levels of corticosterone (CS) have never been analyzed in rats with AE in relation with seizures. Methods. Serum concentration of CS was measured using IBL International Corticosterone ELISA kits in KM rats, rats of the 0 strain, which was selected (based on F2 KM х Wistar hybrids) for the lack of seizures in response to a sound, and Wistar rats. Results. All KM rats developed AE seizures in response to a sound while no seizures were observed in rats of the 0 strain and Wistar rats. The increase in blood CS was observed only in KM rats at 30 min after AE seizure. At background, the level of CS was significantly higher in rats of the 0 strain, which did not develop seizures in response to a sound, than in KM and Wistar rats. CS levels remained unchanged in both 0 and Wistar rats after the sound exposure. Conclusions. The increase in blood CS occurred in KM rats at 30 min after the seizure episode. At background, the CS level was higher in rats of the 0 strain, which did not respond with seizures to a sound, than in Wistar and KM rats. Therefore, the blood level of CS depends in a complicated way on both AE and the selection history of the 0 rat strain., №3 (2019)

We previously showed that cocaine self-administration increases spine density in CA1 hippocampal neurons in Lewis (LEW) but not in Fischer 344 (F344) rats. Dendritic spine morphology is intimately related to its function. Thus, we conducted a 3D morphological analysis of CA1 dendrites and dendritic spines in these two strains of rats. Strain-specific differences were observed prior to cocaine self-administration: LEW rats had significantly larger dendritic diameters but lower spine density than the F344 strain. After cocaine self-administration, proximal dendritic volume, dendritic surface area and spine density were increased in LEW rats, where a higher percentage of larger spines were also observed. In addition, we found a strong positive correlation between dendritic volume and spine morphology, and a moderate correlation between dendritic volume and spine density in cocaine self-administered LEW rats, an effect that was not evident in any other condition. By contrast, after cocaine self-administration, F334 rats showed decreased spine head volumes. Our findings suggest that genetic differences could play a key role in the structural plasticity induced by cocaine in CA1 pyramidal neurons. These cocaine-induced alterations could be related to differences in the memory processing of drug reward cues that could potentially explain differential individual vulnerability to cocaine addiction.

Despite increasing use of intermediate frequency (IF) magnetic fields (MFs) in occupational and domestic settings, scientific evidence necessary for health risk assessments of IF MF is insufficient. Male and female Crl:CD(SD) rats (12 per sex per group) were exposed to 20 kHz, 0.20 mT(root mean square, rms) or 60 kHz, 0.10 mT(rms) sinusoidal MFs for 22 h day−1 for 14 days (acute) or 13 weeks (subchronic). Experiments were duplicated for each frequency to ensure outcome reproducibility, and examinations were blinded for quality assurance. All rats survived without significant clinical signs until the end of experiments. Some changes in body weight between the MF‐exposed and control groups were observed over the course of exposure, although the directions of the changes were inconsistent and not statistically significant after subchronic exposure. There were significant differences between MF‐exposed and control groups in some organ weights and parameters in hematology and clinical chemistry, but these were minor in magnitude and not repeated in duplicate experiments. Histopathological findings reflecting toxicity were sporadic. Frequencies of other findings were similar to historic data in this rat strain, and findings had no specific relationship to changes in organ weight or parameters of hematology and clinical chemistry in each animal. The changes observed throughout this study were considered biologically isolated and were attributable to chance associations rather than to MF exposure. The results, in particular the histopathological evidence, indicate an absence of toxicity in IF MF‐exposed rats and do not support the hypothesis that IF MF exposure produces significant toxicity. Copyright © 2015. The Authors. Journal of Applied Toxicology Published by John Wiley & Sons Ltd., Despite increasing use of intermediate frequency (IF) magnetic fields (MFs) in occupational and domestic settings, scientific evidence is insufficient for IF MF health risk assessments. Rats were exposed to 20 kHz or 60 kHz sinusoidal MFs for 22 h day−1 for 14 days (acute) or 13 weeks (subchronic). MF‐exposed rats did not exhibit significant and reproducible changes in body and organ weights, hematology, clinical chemistry and histopathology. Our results indicate that IF MF exposure does not carry a significant health risk to mammals.

Chronic inflammatory effects of single intratracheal instillation (i.t.) of quartz on rat lung tumorigenesis were examined using 4 different animal models. At first, in order to determine an appropriate dose of quartz i.t. to promote lung tumorigenesis, F344 male rats were administrated single 0, 0.5, 1, 2 or 4 mg quartz/rat after initiation by N-bis(2-hydroxypropyl) nitrosamine (DHPN). Further studies were performed to examine strain differences of the effects of chronic inflammation caused by quartz i.t. in 3 strains of rat, i.e. F344, Wistar-Hannover and SD. Each was instilled with 2mg quartz/rat after DHPN administration and sacrificed in week 24. In addition, strain differences in generation of inflammation were determined at days 1 and 28. Finally, for determination of long-term effects period, F344 and Wistar-Hannover rats were similarly treated, but the experiment was terminated at week 52. In F344 rats, the tumor areas in DHPN treated groups showed a tendency to increase along with the dose of quartz. F344 rats demonstrated the highest and Wistar-Hannover rats the lowest sensitivity to quartz in acute and chronic phases in the 3 strains. In 52 week, in F344 rats, the multiplicity of tumors and the serum concentration of IL-6 in the group treated with DHPN and quartz were significantly increased. The present experiments indicated that chronic inflammation due to quartz instillation exerted promoting effects on lung carcinogenesis in F344, SD and Wistar-Hannover rats. The strain differences in tumor promotion appeared to correlate with inflammatory reactions to quartz and increase of IL-6.

Introduction: Previously observed increased sensitivity to noxious stimulation in the Dahl salt-sensitive rat strain (SS/JrHsdMcwi, abbreviated as SS) compared to Brown Norway rats (BN/NhsdMcwi abbreviated as BN) is mediated by genes on a single chromosome. The current study used behavioral and electrocortical data to determine if differences also exist between SS and BN rats in loss of consciousness. Methods: Behavioral responses, including loss of righting, (a putative index of consciousness) and concurrent electroencephalogram recordings, in 12 SS and BN rats were measured during isoflurane at inhaled concentrations of 0, 0.3, 0.6, 0.8, 1.0 and 1.2%. Results: In SS compared to BN rats, the mean ± SEM EC50 for righting was significantly less (0.65 ± 0.01% vs. 0.74 ± 0.02% inhaled isoflurane) and delta fraction in parietal electroencephalogram was enhanced 50–100% at all isoflurane levels during emergence. The frequency decay constant of an exponential fit of the parietal electroencephalogram spectrum graphed as a function of isoflurane level was three times less steep (mean ± SEM slope −57 ± 13 vs. −191 ± 38) and lower at each level of isoflurane in SS versus BN rats (i.e., shifted toward low frequency activity). Electroencephalogram differences between strains were larger during emergence than induction. Conclusions: Sensitivity is higher in SS compared to BN rats leading to unconsciousness at lower levels of isoflurane. This supports using additional strains in this animal model to study the genetic basis for differences in anesthetic action on mechanisms of consciousness. Moreover, induction and emergence appear to involve distinct pathways.

Using the audiogenic seizure prone Krushinsky-Molodkina rat strain, it was demonstrated that short-term (5 min) exposure of 14-day-old pups to an elevated temperature (42°C) resulted in a significant decrease in audiogenic seizure severity at the age of 1 month. Presumably, this effect is determined by the activation of the heat-shock protein system (stress proteins).

Pappa2 is a metalloproteinase which specifically cleaves IGFBP-3 and IGFBP-5 and in turn releases IGF-1. Recently, we have shown that a subcongenic Dahl salt-sensitive (SS) rat strain containing a 0.71 Mbp of chromosome 13 which includes Pappa2 gene from salt-insensitive Brown Norway (26-P strain) is protected significantly (24 mmHg) from salt-induced hypertension (Cowley et al., 2016). Although it is recognized that Pappa2 modulates development of bone size, cranial cartilage and angiogenesis, its role in kidney development and function is unknown. The present study determined the contribution of Pappa2 to nephron development by comparing SS and 26-P rat strains. It was found that Pappa2 mRNA expression was 5-fold higher in embryonic kidney (day 20.5) of the salt-resistant 26-P rats compared with age-matched SS rats. Pappa2 mRNA expression significantly increased with age of kidney reaching a maximum at postnatal day 5 in both strains. Pappa2 mRNA expression at postnatal day 15 was found to be 9-fold higher in the kidney of 26-P compared with SS strain. Immunohistochemistry studies revealed that Pappa2 co-localized with IGFBP-5 in the ureteric bud indicating that Pappa2 could be important for ureteric branching and nephron endowment. Glomerulus/mm 2 was therefore determined by counting total number of glomeruli in kidney sections from pups starting from P0 to P20. The salt-resistant 26-P congenic strain exhibited significantly greater nephron density 9.03 and 7.07 glo/mm 2 compared to 6.89 and 4.85 glo/mm 2 in SS rat at day P15 and P20, respectively. It appears that the Brown Norway pappa2 allele variant prevents the reduced nephron numbers observed in SS rats and thereby protects these congenic rats from salt-induced hypertension.

Basal divergences in circadian feeding and drinking patterns among different rat strains may bias comparative physiological and pharmacological studies. To examine this issue in detail, Long-Evans (Turku/AB) (L-E) and Han/Wistar (Kuopio) (H/W) rats were monitored with an automated system for seven consecutive days after a habituation period. For the analysis, days were split into hours or into four diurnal periods, and the chronologically repetitive nature of the data was taken into account. While L-E rats displayed two distinct peaks in feeding and drinking that coincided with the light shifts, H/W rats exhibited their lowest consummatory activity at the morning light shift. Further differences were recorded in a number of variables including numbers of meals and drinking episodes as well as their durations. These findings reveal surprisingly wide inter-strain differences. Hence, one should be careful in generalizing ingestive behavioural data obtained from a single rat strain to the entire species.

To confirm the presence of the susceptible gene for the thymoma development in the region that was assumed by the previous linkage study by Oyabu et al. (J Natl Cancer Inst 91:279–282, 1999), we tried to establish a congenic strain of rats. Backcrossings between the BUF/Mna strain as a donor strain and the ACI/NMna strain as an inbred partner were repeated for 12 generations, examining whether rats had the thymoma development region, and then homozygous rats were yielded by mating among the heterozygotes. To detect the phenotypic expression, heterozygous ACI.BUF/Mna-Tsr1/+ (ACI-Tsr1/+) rats were generated by crossing female ACI.BUF/Mna-Tsr1/Tsr1 (ACI-Tsr1/Tsr1) rats with male ACI/NMna rats and were maintained for 24 months. These ACI-Tsr1/+ rats produced thymoma in 71%, showing a dominant trait. The thymomas were of the lymphocyte predominant type, as those developed in rats of the original BUF/Mna strain. Thus, a new rat congenic strain, ACI-Tsr1/Tsr1, was established, revealing that thymoma develops in the dominant trait in ACI-Tsr1/+ rats.

Evaluation of relation between blood pressure (BP) and intraocular pressure (IOP) in two hypertensive rat strains: spontaneously hypertensive rats (SHR) and double transgenic (dTGR) (harboring human renin and angiotensinogen genes) rats, and in their normotensive control Wistar Kyoto and Sprague Dawley rats, respectively.Each rat strain was divided into medicated and non-medicated groups. Medicated rats were treated orally with an angiotensin II receptor type 1 blocker. IOP was measured using a specific rebound tonometer and BP by a tail-cuff method. Both parameters were determined in conscious animals every second week. For comparison, at the end of the study, IOP was measured in conscious and anesthetized rats.The baseline IOP was higher in hypertensive rats vs their normotensive controls. Eight weeks of treatment with an angiotensin type 1 receptor blocker did not prevent a slight increase in IOP, although it abolished the development of hypertension in SHR. The markedly elevated IOP was reduced in medicated and non-medicated dTGR animals during the short follow-up period. General anesthesia reduced IOP significantly.The results suggest a positive relation between BP and IOP in hypertensive rats.

The aims of this study are to investigate the contribution effect of oxidative stress in MK-801-induced experimental psychosis model, and to show that prevention of oxidative stress may improve prognosis. Because oxidative damage has been suggested in the neuropathophysiology of schizophrenia, the possible protecting agents against lipid peroxidation are potential target for the studies in this field. For this purpose, Wistar Albino rats were divided into three groups: the first group was used as control, MK-801 was given to the rats in the second group and MK-801 + ω - 3 essential fatty acids (EFA) was given to the third group. MK-801 was given intraperitoneally at the dose of 0.5 mg/(kg day) once a day for 5 days in experimental psychosis group. In the second group, 0.8 g/(kg day), ω - 3 FA (eicosapentaenoic acid, 18%, docosahexaenoic acid, 12%) was given to the rats while exposed MK-801. In control group, saline was given intraperitoneally at the same time. After 7 days, rats were killed by decapitation. Prefrontal brain area was removed for histological and biochemical analyses. As a result, malondialdehyde (MDA), as an indicator of lipid peroxidation, protein carbonyl (PC), as an indicator of protein oxidation, nitric oxide (NO) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities as antioxidant enzymes, and xanthine oxidase (XO) and adenosine deaminase (AD) activities as an indicator of DNA oxidation was found to be increased significantly in prefrontal cortex (PFC) of MK-801 group (P < 0.0001) compared to control group. In ω - 3 FA treated rats, prefrontal tissue MDA, PC and NO levels as well as SOD, GSH-Px, XO, and AD enzyme activities were significantly decreased when compared to MK-801 groups (P < 0.0001) whereas catalase (CAT) enzyme activity was not changed. Moreover, in the light of microscopic examination of MK-801 groups, a great number of apoptotic cells were observed. ω - 3 FA supplementation decreased the apoptotic cell count in PFC. The results of this study revealed that oxidative stress and apoptotic changes in PFC may play an important role in the pathogenesis of MK-801-induced neuronal toxicity. This experimental study also provides some evidences for the protective effects of ω - 3 FA on MK-801-induced changes in PFC of rats. © 2006.

Earlier, we reported that elevated anxiety-like behavior and high aggression in aged retired breeder Long-Evans (L-E) rats was associated with increased plasma corticosterone and elevated oxidative stress levels. In the present study, we examined how this aged aggressive and anxious rat strain responds to acute sleep deprivation (24 h) and whether their behaviors can be modulated via antioxidant tempol treatment. Four groups of L-E rats were utilized: naïve control (NC), tempol treated control (T+NC), sleep deprived (SD), tempol treated and sleep deprived (T+SD). Thus, two groups were treated with tempol (1mM in drinking water for 2 weeks) while the other two were not. Two groups were subjected to acute sleep deprivation (24 h) using the columns-in-water model while the other two were not. Sleep deprivation induced anxiety-like behavior, led to significant depression-like behavior and short-term memory impairment in SD rats. And, decision-making behavior also was compromised in SD rats. These behavioral and cognitive impairments were prevented with tempol treatment in T+SD rats. Tempol treatment also reduced SD-induced increase in corticosterone and oxidative stress levels in T+SD rats. These results suggest potential involvement of oxidative stress mechanisms in regulation of sleep deprivation induced behavioral and cognitive deficits in male aged-aggressive rats.

Aim: To determine whether two episodes of acute urinary retention lead to additional ischemia-reperfusion injury due to decompression of the bladder, or not. Materials and methods: Sham, retention and recurrent retention groups consisting of 5, 8 and 8 Wistar Albino male rats were randomized, respectively. After the bladders of rats were emptied with 3F catheter, penile urethras were clamped with aneurism clamp and waited for 30 min after diuresis was forced. At the end of this period, penile clamps were removed and the bladder was again decompressed with 3F catheter and after 30 min removed for examination. In the recurrent retention group, the same process was repeated after an interval of one week. Malonedialdehyde (MDA) levels, indicator of lipid peroxidation and myeloperoxidase (MPO) levels, indicator of leukocyte activation, were examined biochemically in the tissues of the removed bladders. Results: In the retention and recurrent retention groups, the average increase in bladder MDA and MPO values was higher than the values of sham group (P < 0.05), however, no significant difference was determined between retention and recurrent retention groups (P> 0.05). Conclusion: In the bladder tissue, due to acute urinary retention and following decompression process, ischemia-reperfusion injury occurs. Two episodes of acute urinary retention do not lead to additional the ischemia-reperfusion injury that develops in the bladder. © Springer 2006.

Predator odors induce unconditioned fear in rats; however, the synthetic predator odor 2,4,5-trimethylthiazoline (TMT) either elicits robust fear behavior (e.g., freezing) or no fear responses at all. The authors investigated whether this is due to the use of different outbred rat strains. TMT induced robust freezing in Sprague-Dawley and Long-Evans rats but not in Wistar rats. All 3 strains avoided TMT, but Wistar rats were less sensitive to TMT. Wistar rats are capable of freezing; all 3 strains displayed the same amount of odor-cue conditioned freezing. Thus, TMT is a robust unconditioned fear stimulus in rats, and prior negative results from other laboratories were due to the choice of a rat strain (Wistar) that is less responsive to TMT.

The effects of immobilization (IM) stress on plasma leptin levels and bodyweight in adult Sprague-Dawley (19 males, 20 females) and Long-Evans (20 males, 20 females) rats were investigated. Following a 10-day baseline period, half the animals from each experimental group were exposed to immobilization stress or no-stress 20 min/day for 21 days. Plasma leptin and corticosterone levels were measured following stress or no-stress exposure on the last day of the experiment. Corticosterone levels confirmed stress exposure. Important interactive effects of stress, strain, and sex on leptin and corticosterone levels were also observed. Specifically, females displayed higher leptin levels than did males, regardless of stress exposure. Strain interacted with stress such that stressed Long-Evans rats displayed higher leptin levels than did stressed Sprague-Dawley rats; there were no strain differences in leptin levels among nonstressed rats. Also, correlations between leptin and corticosterone were strain-specific. Results are discussed with respect to previously unreported strain differences in the effects of immobilization stress on circulating plasma leptin and the relevance to inconsistent findings in the human literature.

We investigated whether changes in noradrenaline neurotransmission in the hypothalamus could explain the hyporesponsiveness of the hypothalamic-pituitary-adrenal (HPA) axis in late pregnancy. Noradrenaline release within the hypothalamic paraventricular nucleus in response to swim stress, as estimated by microdialysis and high-performance liquid chromatography, was lower in 20-day pregnant rats compared to virgin rats. Driving a central noradrenergic pathway using intravenous cholecystokinin increased adrenocorticotropic hormone (ACTH) secretion in virgin rats, but the response was significantly less in 16-day and 20-day pregnant rats. Thus, the activity of noradrenergic inputs to the paraventricular nucleus and the HPA axis is attenuated in late pregnancy. The sensitivity of the HPA axis to noradrenaline in pregnancy was investigated by intracerebroventricular administration of an α1-receptor antagonist, benoxathian, before and during exposure to swim stress. In virgin rats, benoxathian increased basal and stress-induced ACTH secretion, but in late pregnant rats the benoxathian effects were attenuated, indicating reduced sensitivity of the HPA axis to noradrenaline neurotransmission and/or the inability of the system to become disinhibited at this time. α1A-adrenoreceptor mRNA expression in the parvocellular and magnocellular paraventricular nucleus, measured by in situ hybridisation, was decreased in late pregnant compared to virgin rats. Additionally, blocking endogenous opioid inhibition with naloxone pretreatment restored the ACTH secretory response to cholecystokinin in pregnant rats. Thus, in late pregnancy, there is reduced noradrenergic input to the paraventricular nucleus and reduced α1A-receptor expression in the paraventricular nucleus, both of which may contribute to the reduced responsiveness of the HPA axis in pregnancy. © 2005 Blackwell Publishing Ltd.

Genetic variability is an important consideration in the study of the effect of drugs on humans and animals. Specifically, the effect of drugs on behavior varies from one rat strain to another. Methylphenidate (MPI), commonly known as Ritalin, is a psychostimulant with a pharmacological profile similar to amphetamine and cocaine, and is widely used in the treatment of attention deficit/hyperactivity disorder (ADHD). The purpose of this study was to examine the acute dose-response characteristics of MPD on three different male rat strains: spontaneously hypertensive/hyperactive rats (SHR), Wistar-Kyoto (WKY) rats, and Sprague-Dawley (SD) rats. Results showed clear differences in the pattern of behavioral response to the various MPD doses among the three rat strains. The 0.6 mg/kg MPD dose had no effect on any of the strains. At the dose of 2.5 mg/kg MPD, WKY rats reached peak locomotor activity within the initial 10 min, whereas SHR and SD rats reached peak activity in approximately 30 min. Furthermore, the effects on locomotor activity of SHR were longer in duration and higher in locomotor activity, whereas the effects on SD rats were shorter in duration and amplitude. Following the 10.0 mg/kg MPD, WKY, and SD mats reached their peak locomotor activity within 80 min post-injection, whereas SHR reached their peak locomotor activity within the initial 10 min post-injection. In addition, the SHR strain exhibited increased behavioral sensitivity to MPD as expressed by the latency, duration, and amplitude of their response. In conclusion, the dose-response experiment on the acute effects of MPD demonstrated that there are genetic differences in the responses to MPD.

Benzene is used commonly in industry and known as a toxic and carcinogenic agent. In this study a 100 mg.kg-1 dose was administered to Swiss Albino (Rat rattus norvegicus) rats by intraperitoneal injection. Changes in glycogen levels in the liver, muscle and blood glucose levels were investigated after 0, 2, 4, 8, 16, 32 and 64 hours. In this study increased glycogen levels in liver and muscle tissues of both control and benzene-treated rats were found to depend on nourishment. The toxic effect of benzene disappeared at 64 hours after treatment. There was no significant difference between male and female groups regarding glucose levels except at a few time intervals. In conclusion, our results indicate that glycogen levels in the liver and muscle tissues were altered by benzene while glucose in the blood remained largely unchanged.

The normotensive Wistar-Kyoto (WKY) rat strain is a traditional control for the spontaneously hypertensive rat (SHR). We found trait differences between two inbred normotensive WKY strains, derived originally from different vendors, and compared these two strains from La Jolla-Taconic Farms (WKY/lj-tf) and La Jolla-Charles River (WKY/lj-cr) with the inbred SHR/lj-cr for cardiovascular, diurnal, and activity traits under normal and high (8%) NaCl diets. Marked genetic diversity was found between the two vendor-derived WKY. By using an extended study design and radiotelemetry, we compared WKY/lj-cr, WKY/lj-tf, and SHR/lj-cr with the following results: systolic pressure (120 +/- 1, 133 +/- 1, 168 +/- 3 mmHg, respectively); diurnal variation in heart rate (DeltaHR: 46 +/- 3, 71 +/- 4, 57 +/- 2 beats/min, respectively); and salt sensitivity of arterial pressure (Deltasystolic: 10 +/- 1, 21 +/- 1, 20 +/- 1 mmHg, respectively). The WKY/lj-tf genotype apparently results in compromised control of arterial pressure and heart rate, especially during high NaCl intake, and greater susceptibility to high pressure (i.e., high NaCl-induced secondary changes). WKY/lj-tf thus constitutes a new inbred borderline hypertensive WKY substrain offering unique opportunities for genomic studies into the development of genetic hypertension.

Repeated administration of thioacetamide (TA), either intraperitoneally or in drinking water, produced liver cirrhosis in normal Sprague-Dawley rats (SDR) with significant histological alterations similar to those observed in human cirrhosis. In the present study, we evaluated the ability of TA to induce liver cirrhosis in mutant Nagase analbuminaemic SDR. Thioacetamide was administered either intraperitoneally up to 4 months or in drinking water up to 6 months to normal and to Nagase analbuminaemic SDR. Nagase analbuminaemic rats (NAR) were also administered TA in drinking water up to 10 months. Liver cirrhosis development was determined by macroscopic and microscopic analysis. In contrast to normal SDR, no histological characteristics of cirrhosis could be observed in NAR submitted to a 4 or 6 months treatment with TA. Such failure to induce cirrhosis in Nagase rats was confirmed even after prolonged TA administration in drinking water for up to 10 months. In contrast, fibrosis and cholangiolar proliferation occurred in the 10-month TA-treated analbuminaemic rats, suggesting that the mechanisms involved in cirrhosis induction are different from those involved in fibrosis development and carcinogenesis. It is unlikely that the protective effect against TA-induced cirrhosis observed in analbuminaemic rats is related to the absence of albumin in this rat strain, since a co-administration of TA with albumin in analbuminaemic rats did not restore the potential for TA to induce cirrhosis in this rat strain. In conclusion, the fact that induction of cirrhosis by TA is prevented in the inherently hyperlipidaemic and hypercholesterolaemic analbuminaemic rats could be considered for potential application in the treatment of clinical cirrhosis.

The aim of the current study was to investigate the association between expression of acoustic startle response and fear-induced aggression. The intensity of aggressive response towards man and acoustic startle response in adult and 15-day old Norway rats selectively bred for 70 generation for high level or the lack of fear-induced aggression was studied. Adult rats of aggressive strain demonstrated high aggression and increased amplitude of acoustic startle response compared to rats selectively bred for the lack of fear-induced aggression. It was found that, in contrast to infant rats of tame strain, 15-day old rat pups of aggressive strain demonstrated distinct aggressive response towards man, although this response was not as intensive as in adult rats of this strain. There was no considerable difference between aggressive and tame infants in amplitude of acoustic startle response. Significant habituation of startle response was shown in adult rats of aggressive strain, whereas in 15-day old rat pups of aggressive rat strain amplitude of startle response remained unaltered. Both adult and infant rats of tame strain demonstrated considerable habituation of startle response. Thus, defensive aggression in rats with genetic predisposition to fear-induced aggression appears quite early--at eyes opening they demonstrate a pronounced aggressive response toward man. The acoustic startle reflex is one of the elements of complex behavior--fear-induced aggression, and this element is involved in the enhancement of aggressive response towards man in adult rats but does not play any essential role in infant aggressiveness.

Growth curve analyses of laboratory animals, such as the mouse and rat, provide a biological model for an understanding of overall growth of the body and its components. The body weight of inbred laboratory mice reaches a plateau of growth curve without obvious variance during adulthood after 9 weeks old [Growth chart of inbred mice (A) BALB/cJ (Stock number: 000651); (B) C57BL/6 J (Stock number: 000664) (data from The Jackson Laboratory Inc., USA, http://jaxmice.jax.org)]. Differently, overall body weight of rat postnatally increases in linear growth irrespective of rat strain or gender although body weight of female rat is always lower than that of male at the same age. The weight of male/female rat (Sprague-Dawley, Dark Agouti, and Lewis) is normally above 190/130 g after 9 weeks old (adulthood) according to the growth curves from Harlan Laboratories Inc., USA (http://www.harlan.com) [Growth chart of inbred rats (A) Lewis/HanHsd-Harlan Nederland; (B) Hsd: Sprague Dawley SD-Harlan Nederland (data from Harlan Laboratories Inc., USA, http://www.harlan.com)]. The linear growth type of rat will cause an apparent body weight difference and different size of transplant organs as the rats at two different stages are chosen for scientific studies. The relationship between body weight of donor or recipient and short-term, long-term isograft/allograft function has been studied by a series of experimental investigations.

1. The aim of this study was to compare the effects of acute amphetamine (AMPH) treatment and restraint stress on plasma level of prolactin (PRL) and PRL mRNA expression in the adenohypophysis in Sprague–Dawley and Lewis male rats, the latter known to have a deficient hypothalamo–pituitary-adrenal (HPA) axis.

Background. Hypercholesterolemic Imai rats, especially males, spontaneously develop proteinuria and glomerulosclerosis. We previously studied the effect of estrogen on the development of glomerular injury in this rat strain and found that estrogen treatment showed a sex difference in its effect on glomerular injury, exerting dual effect, an attenuating effect in males and an exacerbatory effect in females. Because this dual effect seemed to be related to and regulated by testosterone, in the present study, we investigated whether estrogen's effect on glomerular injury differed in the presence and absence of testosterone, using castrated male Imai rats in experiment 1 (Exp 1), and testosterone-replaced castrated Imai rats in Exp 2.

A polycystic kidney rat model is being established from a Crj:CD (SD) rat strain. Unlike existing animal models of polycystic kidney disease, this mutant rat has a completely polycystic liver. Mating experiments revealed that the phenotype is controlled by an autosomal recessive gene. We propose that this gene be tentatively called the "rpc" gene.

Inbred carcinogen-resistant DRH rat strain developed from the closed colony Donryu rats on the basis of selective markers such as poor induction of gamma-glutamyltranspeptidase and marked reduced incidences of liver tumors during 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) administration, which took more than 10 years. Previously, we observed that the Donryu rat liver was quite sensitive to both DNA-damaging and cytotoxic effects of 3'-Me-DAB, while the DRH rat liver showed tolerance to 3'-Me-DAB under the same conditions. In the present study, we examined mRNA levels related to the cytotoxic drug resistance mechanism in the livers of DRH and Donryu rats using RT-PCR. Contrary to our expectation, we observed rather similar levels of mRNAs between the two rat strains under the following conditions: i) mdr1 mRNA induction after 3'-Me-DAB administration. ii) MLP-2 mRNA reduction by 3'-Me-DAB administration, iii) MLP-2 mRNA induction after cholestasis and iv) constitutive levels of cMOAT gene expression. On the other hand, the levels of p53 mRNA and p53 protein in the Donryu rat liver were higher than those in DRH rat liver during 3'-Me-DAB administration, suggesting that the former were more sensitive to 3'-Me-DAB than DRH rat under these conditions. In conclusion, we failed to demonstrate the difference in the cytotoxic drug resistance mechanism between DRH and Donryu rats at least under the conditions examined in this study.

Fischer 344 (F344) and Lewis (LEW) rats show considerable neuroanatomical and neurophysiological differences within the mesolimbic dopamine system. The aim of our experiments was to study the functional correlates of such differences by examining open-field behavior and the sensitivity towards the psychostimulant and rewarding effects of amphetamine in male and female, F344 and LEW rats. In addition, the consequences of short versus extended habituation to open-field testing on amphetamine locomotion in these two rat strains was assessed. LEW but not F344 rats irrespective of gender showed between-session habituation of open-field activity. Amphetamine-induced locomotion was higher in F344 compared to LEW rats and in females compared to male rats. In addition, extended habituation increased the locomotor effects of amphetamine. The rewarding effects of amphetamine as measured by the conditioned place preference test were more pronounced in F344 than in LEW rats. Our results suggest that the two rat strains differed in their behavioral response to mild stress and to amphetamine and that these differences may depend upon differences within the mesolimbic dopamine system.

Male and female Fawn Hooded rats were examined for conditioned place preference (CPP) or aversion (CPA) to lysergic acid diethylamide (LSD). Using a biased design, experimental animals were trained with LSD (0.2 mg/kg, I.P.) administered in conjunction with confinement in either the preferred or nonpreferred location. Control animals received confinement in both locations after administration of saline. Results indicated that rats administered LSD while sequestered in the nonpreferred location spent more time in that location during a nondrug test. This effect, indicative of a conditioned place preference, was exhibited only in male animals. Results are discussed in terms of potential sex differences that may mediate serotonergic sensitivity in the Fawn Hooded rat strain.

Background Even though more than 600 stroke treatments have been shown effective in preclinical studies, clinically proven treatment alternatives for cerebral infarction remain scarce. Amongst the reasons for the discrepancy may be methodological shortcomings, such as high mortality and outcome variability, in the preclinical studies. A common approach in animal stroke experiments is that A) focal cerebral ischemia is inflicted, B) some type of treatment is administered and C) the infarct sizes are assessed. However, within this paradigm, the researcher has to make numerous methodological decisions, including choosing rat strain and type of surgical procedure. Even though a few studies have attempted to address the questions experimentally, a lack of consensus regarding the optimal methodology remains. Methods We therefore meta-analyzed data from 502 control groups described in 346 articles to find out how rat strain, procedure for causing focal cerebral ischemia and the type of filament coating affected mortality and infarct size variability. Results The Wistar strain and intraluminal filament procedure using a silicone coated filament was found optimal in lowering infarct size variability. The direct and endothelin methods rendered lower mortality rate, whereas the embolus method increased it compared to the filament method. Conclusions The current article provides means for researchers to adjust their middle cerebral artery occlusion (MCAo) protocols to minimize infarct size variability and mortality. Funding Agencies|County Council of Ostergotland, Sweden

We have previously shown interstrain variation (indicating a genetic basis), and intrastrain variation in survival time after hemorrhage (STaH) among inbred rat strains. To assist in understanding physiological mechanisms associated with STaH, we analyzed various arterial blood measures (ABM; pH, Paco2, oxygen content, sodium, potassium, glucose, bicarbonate, base excess, total CO2, and ionized calcium) in inbred rats. Rats from five inbred strains ( n = 8–10/strain) were catheterized and, ∼24 h later, subjected to a conscious, controlled, 47% hemorrhage. ABM were measured at the start (initial) and end (final) of hemorrhage. Inter- and intrainbred strain variations of ABM were quantified and compared, and correlations of ABM with STaH were determined. All final ABM values and some initial ABM values were different among strains. Most ABM changed (Δ) during hemorrhage, and these changes differed among strains ( P < 0.03). Some strain-dependent correlations ( r ≥0.7; P ≤ 0.05) existed between ΔABM and STaH (e.g., BN/Mcwi, ΔK+, r = −0.84). Dark Agouti rats (longest STaH) had the smallest ΔPaco2, ΔHCO3−, and Δbase excess, and the highest final glucose. High coefficients of variation (CVs, >10%), strain-specific CVs, and low intraclass correlation coefficients ( rI< 0.5) defined the large intrastrain ABM variation that exceeded interstrain variation for most ABM. These results suggest that some ABM (K+, Paco2, glucose, oxygen content) could predict subsequent STaH in an inbred rat strain-dependent manner. We speculate that whereas genetic differences may be responsible for interstrain variation, individual-specific epigenetic processes (e.g., DNA methylation) may be partly responsible for both inter- and intrastrain ABM variation.

The effects of lowering blood pressure (BP) by hydralazine (HY) (2 mg/kg) on spontaneous (SA) and post-sigh (PSA) sleep apneas have been studied in spontaneously hypertensive (SHR) rats by monitoring their respiration and sleep by the EEG for 6 hours. Normotensive Wistar-Kyoto (WKY) rats, from which the SHR rat strain was derived, were used as an appropriate control. The SHR rats had more SA (p < 0.02) and PSA (p < 0.0001) apneas/hour than WKY rats during nonrapid eye movement sleep and their mean BP was higher by 40 mm Hg (p < 0.0001) than WKY rats. Administration of HY to SHR rats equalized their BP with the arterial pressure of WKY rats and reduced the SA and the PSA apneas/hour to equivalence with WKY normotensive rats. These results demonstrate that even in the context of lifelong hypertension, acute normalization of BP significantly reduces sleep apneas in rats. They further suggest that improved management of BP may be of clinical benefit to patients with apnea who have long-standing hypertension.

The propensity to recall unpleasant events may be related to depression and posttraumatic stress disorder. This study examined the extent to which the recall of a previously unpleasant event (i.e., passive avoidance training) may be influenced by another aversive event. The other aversive event was tail shock. Since the Wistar Kyoto (WKY) rat strain has been proposed as an animal model of depressive behavior, this study was conducted with WKY and Wistar rats. Parameters manipulated included shock controllability, shock sequence (i.e., tail shock before avoidance training versus tail shock after training), and rat strain. Performance of the passive avoidance (PA) response was greater in WKY rats. Exposure to inescapable tail shock was related to greater PA performance compared to exposure to escapable or no-shock treatments. Tail shock prior to PA training led to a greater recall of the PA response. The magnitude of the PA response was influenced by the rat strain, shock controllability, and shock sequence. The applicability of these data to the memory bias phenomenon in depression is discussed.

A decrease in the total count of follicles in the diestrus and proestrus and higher incidence of permanent estruses were found in 3-month-old females of the catatonic GC rat strain in comparison with Wistar females (control). At the age of 6-12 months, GC females had lower incidence of long estrus and diestrus. The estrous cycle of GC females was shorter than of Wistar rats. With aging (at the age of 18 months), the counts of growing and maturing follicles signifi cantly decreased. Higher counts of growing single-layer and bilayer follicles were found in 18-month-old GC females. Differences in the length of estrus and diestrus and in the incidence of abnormal phases in the two strains also disappeared at this age. Selection by high catatonic reactivity was associated with a decrease in body weight.

Our previous studies have shown that Tm values for tauroursodeoxycholate (TUDC) and tauro beta-muricholate (T beta-MC) are more than two-fold higher than that for taurocholate (TC) in the rat. The present study attempted to clarify whether tauro alpha-muricholate (T alpha-MC) also has such an unusually large Tm value in the rat. Under nembutal anesthesia, male Wistar derived rats (body weight 280-300 g, 13 wks in age) were continuously infused with T alpha-MC solution. The infusion rate was raised stepwise every 20 min, until the bile flow began to decline. Bile was collected every 10 min and bile salt excretion rate was determined. The average of the highest three excretion values was assumed to be the Tm in each animal. The Tm value of T alpha-MC was found to be 2.86 +/- 0.36 mumol/min/100 g (mean +/- SD, n = 4), which was even greater than Tm values for TUDC (2.59 +/- 0.39 mumol/min/100 g, n = 4) and T beta-MC (1.93 +/- 0.31 mumol/min/100 g, n = 4) as we reported previously. The relationship between the bile flow rate (microliter/min/100 g, Y axis) and bile salt excretion rate (mumol/min/100 g, X axis) was highly linear [Y = (6.00 +/- 0.29) x +(6.60 +/- 1.88), P0.001, r = 0.95, n = 54]. The slope value for T alpha-MC (6.00 +/- 0.29 microliters/mumol) was significantly higher than that for TUDC (4.76 +/- 0.71 microliters/mumol) and was comparable to that for T beta-MC as we previously found for these bile salts in this rat strain. The results suggest that T alpha-MC has a very efficient transport system in this species as was observed for the other two bile salts that have a 7 beta-hydroxy group (TUDC and T beta-MC). This efficient transport system thus appears to be shared not only by bile salts specifically having a 7 beta-hydroxy group, but also by other bile salts such as T alpha-MC that have a 6 beta-hydroxy group but not a 7 beta-hydroxy group.

Recently, the existence of a rat strain exhibiting autosomal dominant polycystic kidney disease (PKD) resembling human PKD has been described. An exact description of the course of chronic renal failure in this strain, however, is still missing. Thus the aim of this study was to analyze the long-term course of renal failure in these rats. In addition, unilateral nephrectomy (UNX) was performed in order to evaluate the impact of UNX on the occurrence of uremia. Our data clearly revealed that 70-80% of all animals of this rat strain developed uremia within 21 months. Additionally, proteinuria and hypercholesterolemia occurred, while the blood pressure was fairly unaffected. Also a slight degree of anemia was noted. In this long-term study death was due to uremia. The median survival time was significantly shorter in UNX PKD (median 11.6 months) than in non-UNX PKD animals (17.0 months; log-rank test: p = 0.001).with respect to renal function this rat model resembles human PKD disease. Furthermore, we could demonstrate that UNX is suitable to accelerate the rate of progression of renal failure in this model.

Previous studies in rats and humans have shown that the essential amino acid tryptophan (TRP) is depleted after consumption of a gelatin-based protein-carbohydrate mixture, which is lacking L-tryptophan (TRP−). In rats, TRP depletion caused impaired object recognition but only had a modest effect on affective behaviour. Because these studies were preformed with Wistar rats, the aim of the present experiment was to evaluate strain differences in behavioural responses to acute TRP depletion between Brown Norway (BN) and Sprague Dawley (SD) rats. The rats were repeatedly treated with TRP− or a balanced control (TRP+) and were tested in tests of anxiety- and depression-related behaviour (open-field test, home cage emergence test, social interaction test, forced swim test) and memory. SD rats, but not BNs, showed more anxiety- and depression-related behaviour and impaired object recognition after TRP− treatment. There was a dissociation between plasma TRP levels, central 5-HT concentrations and 5-HIAA/5-HT turnover. Both strains showed about 60% decrease in plasma TRP/ΣLNAA levels, whereas hippocampal 5-HT levels were lower after TRP− in BN but not SD rats. Conversely, 5-HIAA/5-HT turnover was lower after TRP− in SD but not BN rats, suggesting a dissociation between 5-HT storage and release in SDs. The present study suggests that acute tryptophan depletion effects are strain dependent on the behavioural and the neurochemical level.

BackgroundIn humans, salt intake has been suggested to influence blood pressure (BP) on a wide range of time scales ranging from several hours or days to many months or years. Detailed time course data collected in the Dahl salt-sensitive rat strain suggest that the development of salt-induced hypertension may consist of several distinct phases or components that differ in their timing and reversibility. To better understand these components, the present study sought to model the dynamics of salt-induced hypertension in the Dahl salt sensitive (Dahl-S) rat using 3 sets of time course data.ResultsThe first component of the model ("Acute-Reversible") consisted of a linear transfer function to account for the rapid and reversible effects of salt on BP (ie. acute salt sensitivity, corresponding with a depressed slope of the chronic pressure natriuresis relationship). For the second component ("Progressive-Irreversible"), an integrator function was used to represent the relatively slow, progressive, and irreversible effect of high salt intake on BP (corresponding with a progressive salt-induced shift of the chronic pressure natriuresis relationship to higher BP levels). A third component ("Progressive-Reversible") consisted of an effect of high salt intake to progressively increase the acute salt-sensitivity of BP (ie. reduce the slope of the chronic pressure natriuresis relationship), amounting to a slow and progressive, yet reversible, component of salt-induced hypertension. While the 3 component model was limited in its ability to follow the BP response to rapid and/or brief transitions in salt intake, it was able to accurately follow the slower steady state components of salt-induced BP changes. This model exhibited low values of mean absolute error (1.92 ± 0.23, 2.13 ± 0.37, 2.03 ± 0.3 mmHg for data sets 1 - 3), and its overall performance was significantly improved over that of an initial model having only 2 components. The 3 component model performed well when applied to data from hybrids of Dahl salt sensitive and Dahl salt resistant rats in which salt sensitivity varied greatly in its extent and character (mean absolute error = 1.11 ± 0.08 mmHg).ConclusionOur results suggest that the slow process of development of salt-induced hypertension in Dahl-S rats over a period of many weeks can be well represented by a combination of three components that differ in their timing, reversibility, and their associated effect on the chronic pressure natriuresis relationship. These components are important to distinguish since each may represent a unique set of underlying mechanisms of salt-induced hypertension.

Immunosenescence or dysregulation of the immune system may accelerate the aging process and shorten the lifespan in animals. Calorie restriction, a well-known nutritional intervention for longevity in laboratory animals, retards immunosenescence and modulates the immunosystem. These effects of CR could contribute partly to extending the lifespan. A transgenic (Tg) dwarf rat strain, in which the growth hormone (GH) axis is selectively suppressed, lived longer and exhibited several phenotypes similar to those in CR rats, suggesting an important role for the GH axis in the effect of CR. Here, we describe the longevity, pathology, thymic and splenic lymphocyte subpopulations and response to endotoxin in Tg rats in comparison with CR rats. The findings support the importance of the GH axis in the effect of CR on the immune system and, in particular, longevity. The Tg rats could be a useful tool to better understand the molecular mechanisms underlying the antiaging effect of CR.

The highly toxic environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was recently reported to decrease serum melatonin levels throughout the circadian cycle in the most TCDD-susceptible strain of rat, Long-Evans. To find out whether this effect is related to the mechanism of acute lethality of TCDD, serum melatonin levels were measured at the nocturnal peak phase in the most TCDD-resistant rat strain variant, Han/Wistar rats, 6 hr to 28 days after TCDD exposure. The same dose as used in the previous study, 50 micrograms/kg, decreased serum melatonin levels to approximately half the control values by the first day after the treatment. Melatonin concentrations remained at this reduced level over the whole observation period. In an auxiliary experiment, Han/Wistar rats were dosed with 1000 micrograms/kg TCDD and killed on day 3. Neither light nor electron microscopic examination of their pineal glands revealed any alteration attributable to TCDD treatment. These findings might indicate that the reduction of serum melatonin levels in the rat by TCDD is not related to its lethal effect and is not due to a direct damage of the pineal gland.

To determine whether the increased renal biosynthesis of thromboxane A2 observed in young genetically hypertensive rats of the Lyon strain could be involved in the development of their hypertension, Lyon hypertensive female rats received either thromboxane synthetase inhibitors (Dazmegrel or OKY 046) or a thromboxane A2 receptor antagonist (AH 23848) during their prehypertensive stage. Treatment from 5 to 9 weeks of age with Dazmegrel failed to reduce systolic blood pressure. When given from 3 to 9 weeks of age, Dazmegrel and OKY 046 induced a similar progressive and specific reduction (60%) in the urinary excretion of thromboxane B2 that was associated with a transient decrease in blood pressure level with Dazmegrel and a longer lasting blood pressure-lowering effect with OKY 046. AH 23848, given according to the same schedule, normalized the blood pressure level. This effect persisted 1 week after the cessation of the treatment. Interestingly, active doses of thromboxane synthetase inhibitors or of thromboxane A2 receptor blocker required a 3-week delay to exhibit their antihypertensive properties. It is concluded that 1) the elevated production of thromboxane A2 observed in young Lyon hypertensive rats is likely to participate actively in their blood pressure regulation and 2) this effect may be independent of its direct vasoconstrictor properties.

11beta-Hydroxysteroid dehydrogenase activity in the kidneys of NISAG rats (rat strain with hereditary stress-induced arterial hypertension) was 1.5-fold higher than in WAG rats. An inverse relationship was observed in the liver of these animals. After stress exposure 11beta-hydroxysteroid dehydrogenase activity remained unchanged in the kidneys of NISAG and WAG rats, but significantly increased in the liver of NISAG rats. Functional activity of 11beta-hydroxysteroid dehydrogenase probably reflects the hypertensive state of NISAG rats.

Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are closely related molecules. Insulin-like growth factor-binding protein-3 (IGFBP-3) is a main molecule that binds IGF-I. GH, IGF-I and IGFBP-3 have important roles in growth and development. In this study, we investigated the effects of exercise during pregnancy on maternal plasma levels of GH, IGF-I and IGFBP-3 and on fetal development. We also recorded the weights of placenta, lengths of umbilical cord, fetal body weights, fetal heights, and weights of fetal tissues. Pregnant Wistar Albino rats were divided into two groups: exercise and control groups (n = 7 for each). A treadmill exercise was performed as 20 m/min for 20 min/day, once per day for 19 days in exercise group. Blood samples were collected from pregnant rats on 0, 7th, 14th and 20th days of gestation (D) under anesthesia with intracardiac puncture, and maternal plasma levels of GH, IGF-I and IGFBP-3 were determined. Fetuses were taken with cesarean section on D20, and various parameters for fetal growth were measured. Plasma GH and IGF-I levels were elevated in exercising pregnant rats on D14 and D20, respectively, when compared to controls, and IGFBP-3 levels were increased on D14 and D20. Among the growth parameters examined, only fetal body weights and weights of fetal liver were significantly decreased in the exercise group (p < 0.01 and p < 0.05, respectively). These results indicate that maternal exercise significantly increases plasma levels of GH, IGF-I and IGFBP-3 in the late period of pregnancy but causes adverse effects on fetal growth. © 2006 Tohoku University Medical Press.