Hypertension during chronic exposure to cold: comparison between Sprague-Dawley and Long-Evans strains.

It is now well established that chronic exposure of rats to cold (5-6 degrees C) induces an elevation of systolic, diastolic, and mean blood pressures and cardiac hypertrophy within 3 weeks. Since rats of the Long-Evans (LE) strain are known to be resistant to the induction of deoxycorticosterone salt induced hypertension, their cardiovascular responses to chronic exposure to cold were compared with those of rats of the Sprague-Dawley (SD) strain. The results of these studies revealed clear differences between the LE and SD strains of rats. Thus, rats of the SD strain had a significant elevation in their blood pressure; a significantly increased urinary output of norepinephrine and epinephrine; a significantly greater dipsogenic responsiveness to acute administration of angiotensin II, and significant increases in weights of the heart, kidneys, adrenals, and brown adipose tissue compared with their warm-adapted controls. All of these changes are characteristic of rats acclimated to cold. In contrast, rats of the LE strain appear to be less responsive to cold in that blood pressure failed to rise as sharply and to attain as high a level. Furthermore, urinary outputs of norepinephrine and epinephrine were significantly lower in cold-treated rats of the LE strain compared with cold-treated rats of the SD strain, but dipsogenic responsiveness to angiotensin II was unchanged. Although increases in the weight of the previously mentioned organs were also observed in cold-treated rats of the LE strain compared with their warm-adapted controls, weights of the heart and interscapular brown adipose tissue of both groups were significantly less than those of counterparts of the SD strain.(ABSTRACT TRUNCATED AT 250 WORDS)     

Brain vessels in the rats exposed to primary and repeated tail-suspension. Minimization of structural changes after repeated exposure

The aim of study was histological examination of brain vessels in the rats exposed to repeated tail-suspension (TS). The rats were subjected to 30-day TS, then readapted to horizontal position for 30 days and again exposed to 14-day TS simultaneously with the rats which were underwent to 14-day TS for the first time. 30-day TS induced in brain vessels the adaptive changes hindering the excessive blood inflow to brain--spasm and hypertrophy of muscle-elastic valves in extra- and intracerebral arteries and also the destructive changes--loss of vascular tone in extra- and intracerebral arteries, plethora in extra- and intracerebral veins, intracerebral venules and capillaries, conglutination of erythrocytes in capillaries, plasmatization of veins and capillaries and edema of brain tissue pointing out in total the increase in blood inflow to the brain and difficulty of blood outflow. After 30-day readaptation of TS-rats to horizontal position only adaptive changes in extracerebral arteries and intracerebral capillaries (cell proliferation) and edema of brain tissue were revealed. After repeated, 14-day TS in spite of new redistribution of blood to the head, in contrast to the vessel alterations after primary 14-day TS, the adaptive and destructive changes in brain vessels were lack, excluding only moderate plethora of intracerebral veins, cell proliferation in capillaries and weak signs of edema.     

The effect of repeated reproduction on the incidence of pituitary tumours in Wistar rats

Weanling female litter mates were equally proportioned at the start of the study between a breeding and a non-breeding group. At 10 weeks of age, each rat of the breeding group was housed individually with a male until 5 litters were produced (or exceptionally for a maximum of 42 weeks) before the male was removed. Females of the non-breeding group were kept singly in similar cages. 2 years after the start of the study all the surviving rats of both groups were killed. Comprehensive necropsies were performed on the decedents and survivors and the pituitary gland of each rat was examined histologically. The 48% survival of the female rats which were allowed to breed was better, but not significantly so, than the 38% of those not allowed to breed. Overall fewer, 70% (35 of 50) of the mated female rats had pituitary tumours compared with 80% (40 of 50) of the non-mated group. Fewer of the decedents, 69% (18 of 26), of the mated females had pituitary tumours compared with 94% (29 of 31) in the decedents of the non-mated group. More survivors, 71% (17 of 24), of the mated females had pituitary tumours compared with 58% (11 of 19) of the surviving non-mated rats. A tumour was first observed at day 328 in the non-mated group, whilst in the mated group the first tumour was identified at day 450. It is suggested that breeding delays the appearance of pituitary tumours in the female rat.     

Duration of protection from reinfection following exposure to sialodacryoadenitis virus in Wistar rats

Wistar rats [Cr1:(WI)BR] were inoculated intranasally with approximately 10(3) median mouse lethal infective doses of sialodacryoadenitis (SDA) virus. Animals were subsequently selected at random, removed to a separate isolation room, and reinfected with SDA virus at 3, 6, 9, 12 or 15 months. Pre- and postinoculation serum samples were collected from all animals during the course of the study and evaluated for antibody titers to SDA virus. All experimental, control and sentinel animals, following inoculation with SDA virus, were necropsied and examined for lesions consistent with SDA. Salivary gland lesions were minimal to absent in rats reinfected with SDA virus for up to 12 to 15 months after the initial exposure and minimal to moderate in the respiratory tract at 12 or 15 months. SDA-associated lesions were extensive in age matched control animals examined at each time period of reinfection with SDA virus. Thus, prior exposure to SDA virus did protect against the development of typical salivary gland lesions for up to 15 months. Recovered animals were evaluated for their ability to transmit the virus following reinfection. Rats reinfected at 6 or 9 months were infectious to their naive cage mates. The results indicate that reinfection with homologous rat coronavirus can occur as early as 6 months after the initial infection, and such rats can transmit the infection to contact controls.     

Behavioral and cross sensitization after repeated exposure to modafinil and apomorphine in rats

Repeated exposure to psychostimulant drugs has been known to produce behavioral sensitization, a phenomenon explicitly indexed by locomotion (LM) and stereotyped movements (SM). So far, no evidence has demonstrated that this phenomenon can be displayed following the administration of modafinil (MOD) in animal study. We, therefore, assessed the possibility of behavioral sensitization of MOD and a direct dopamine agonist, apomorphine (APO), and cross-sensitization of these two drugs with one other. Pretreatment with MOD (64 mg/kg) or APO (0.5 mg/kg or 1.0 mg/kg) for 10 consecutive days was followed by a short-term (3 days) or long-term (21 days) withdrawal. Rats were then challenged with the drug and reciprocally re-challenged with the counterpart drug. The results showed that following short-term and long-term washout periods, both MOD and APO successfully induced sensitization in LM and SM. There was no cross-sensitization; an even lesser magnitude in LM when MOD-sensitized rats were challenged with APO was observed. However, after both the short-term and long-term withdrawal periods, APO (1.0 mg/kg)-sensitized rats showed cross-sensitization in LM and SM to MOD (64 mg/kg) challenge. The magnitude of APO-MOD cross-sensitization was lesser than the behavioral sensitization induced by APO alone. Our results indicated behavioral sensitization could be induced in rats exposed to MOD. In addition, changes in dopaminergic receptor activities could be involved in cross-sensitization of APO to MOD but not vice versa.     

Macromolecular MRI contrast agents with small dendrimers: pharmacokinetic differences between sizes and cores

Large macromolecular MRI contrast agents with albumin or dendrimer cores are useful for imaging blood vessels. However, their prolonged retention is a major limitation for clinical use. Although smaller dendrimer-based MRI contrast agents are more quickly excreted by the kidneys, they are also able to visualize vascular structures better than Gd-DTPA due to less extravasation. Additionally, unlike Gd-DTPA, they transiently accumulate in renal tubules and thus also can be used to visualize renal structural and functional damage. However, these dendrimer agents are retained in the body for a prolonged time. The purpose of this study was to obtain information from which a macromolecular dendrimer-based MRI contrast agents feasible for use in further clinical studies could be chosen. Six small dendrimer-based MRI contrast agents were synthesized, and their pharmacokinetics, whole-body retention, and dynamic MRI were evaluated in mice to determine an optimal agent in comparison to Gd-[DTPA]-dimeglumine. Diaminobutane (DAB) dendrimer-based agents cleared more rapidly from the body than polyamidoamine (PAMAM) dendrimer-based agents with the same numbers of branches. Smaller dendrimer conjugates were more rapidly excreted from the body than the larger dendrimer conjugates. Since PAMAM-G2, DAB-G3, and DAB-G2 dendrimer-based contrast agents showed relatively rapid excretion, these three conjugates might be acceptable for use in further clinical applications.     

Comparison of the reactions of male and female Wistar rats. To 5-day exposure to 2G hypergravity

Number of essential distinctions between male and female rats both before and after 5-day exposure to 2g were observed. These distinctions are not simple quantitative. One gets an impression that males and females have various "strategies" of homeostasis maintenance in the norm and various patterns of adaptive reactions in different situations including 2g hypergravity.     

Genetic variability within and between outbred Wistar strains of rats.

The allelic frequencies at 6 isozyme loci (Es-1, Es-2, Es-3, Es-4, Es-Si and Amy-1) were examined in 4 outbred Wistar strains and additionally 2 SD strains as controls. From the allelic frequencies, the averages of the heterozygosities in individual strains and the geometric genetic distances between every pair of all possible strain combinations were calculated. The averages of the heterozygosities in 2 SD strains were both intermediate (around 0.2) and the genetic distance between them was rather short. But among the Wistar strains, the averages of the heterozygosities were highly variable and the genetic relationships among them were very variable in their genetic distances. From these results, it was suggested that the outbred Wistar strains were different each other in their genetic constitutions and that no suggestion was obtained to descriminate genetically the Wistar strains from the SD strains.     

Decreased level of Nurr1 in heterozygous young adult mice leads to exacerbated acute and long-term toxicity after repeated methamphetamine exposure

The abuse of psychostimulants, such as methamphetamine (METH), is prevalent in young adults and could lead to long-term adaptations in the midbrain dopamine system in abstinent human METH abusers. Nurr1 is a gene that is critical for the survival and maintenance of dopaminergic neurons and has been implicated in dopaminergic neuron related disorders. In this study, we examined the synergistic effects of repeated early exposure to methamphetamine in adolescence and reduction in Nurr1 gene levels. METH binge exposure in adolescence led to greater damage in the nigrostrial dopaminergic system when mice were exposed to METH binge later in life, suggesting a long-term adverse effect on the dopaminergic system. Compared to naïve mice that received METH binge treatment for the first time, mice pretreated with METH in adolescence showed a greater loss of tyrosine hydroxylase (TH) immunoreactivity in striatum, loss of THir fibers in the substantia nigra reticulata (SNr) as well as decreased dopamine transporter (DAT) level and compromised DA clearance in striatum. These effects were further exacerbated in Nurr1 heterozygous mice. Our data suggest that a prolonged adverse effect exists following adolescent METH binge exposure which may lead to greater damage to the dopaminergic system when exposed to repeated METH later in life. Furthermore, our data support that Nurr1 mutations or deficiency could be a potential genetic predisposition which may lead to higher vulnerability in some individuals.     

Physiological dependency between the hypothalamus and the thymus in Wistar rats. II. The neurosecretion level and microstructural changes following para-chlorophenylalanine administration. The differences in DL-5-hydroxy G-3H tryptophane incorporation in the hypothalamus of normal and thymectomized rats

The experiments were carried out on male Wistar rats, both normal and thymectomized in which the thymus was excised in 12th h of life. 8 weeks later, the animals were administered parachlorophenylalanine [PCPA], i.e. a compound inhibiting tryptophane hydroxylase, in the amount of 200 mg/kg of body weight. The studied hypothalamus preparations, i.e. supraoptical [NSO] and paraventricular nuclei [NPV] revealed an increased level of Gomori-positive neurosecretory material in thymectomized rats when compared to control animals. It was observed that the former rodents manifested an elevated incorporation of the isotope, i.e. DL-5-Hydroxy [G-3H] Tryptophane. The calculations performed by the use of the Gosset's t-test ("Student's") showed that the difference was statistically significant (p less than 0.001).     

Gender differences in oxidative stress in spinal cord of rats submitted to repeated restraint stress

Behavioral and neurochemical gender-specific effects have been observed following repeated stress. The aim of this study is to verify the effects of repeated restraint stress on free radical production (evaluated by DCF test), lipoperoxidation (evaluated by TBARS levels), and total antioxidant reactivity (TAR) in the spinal cord of male and female rats. Results demonstrate no effect on lipoperoxidation; chronic stress decreased TAR both in male and female spinal cord. In addition, gender differences were observed both in TAR and in the production of free radicals, both being increased in females. These results may be relevant to the gender-specific differences observed after exposure to repeated stress.     

Decreased reward sensitivity in rats from the Fischer344 strain compared to Wistar rats is paralleled by differences in endocannabinoid signaling

Background

The aim of the present study was to examine if differences in the endocannabinoid (ECB) system might be linked to strain specific variations in reward-related behavior in Fischer344 (Fischer) and Wistar rats.

Methodology/Principal Findings

Two rat strains, the Fischer and the Wistar strain, were tested for different aspects of reward sensitivity for a palatable food reward (sweetened condensed milk, SCM) in a limited-access intake test, a progressive ratio (PR) schedule and the pleasure-attenuated startle (PAS) paradigm. Additionally, basic differences in the ECB system and cannabinoid pharmacology were examined in both rat strains. Fischer rats were found to express lower reward sensitivity towards SCM compared to Wistar rats. These differences were observed for consummatory, motivational and hedonic aspects of the palatable food reward. Western blot analysis for the CB1 receptor and the ECB degrading enzyme fatty acid amide hydrolase (FAAH) revealed a lower expression of both proteins in the hippocampus (HPC) of Fischer rats compared to the Wistar strain. Furthermore, increased cannabinoid-stimulated extracellular-regulated kinase (ERK) phosphorylation was detected in Wistar rats compared to the Fischer strain, indicating alterations in ECB signaling. These findings were further supported by the pharmacological results, where Fischer rats were found to be less sensitive towards the effects of the CB1 receptor antagonist/inverse agonist SR141716 and the cannabinoid agonist WIN 55,212-2.

Conclusions/Significance

Our present findings indicate differences in the expression of the CB1 receptor and FAAH, as well as the activation of ECB signaling pathways between Fischer and Wistar rats. These basic differences in the ECB system might contribute to the pronounced differences observed in reward sensitivity between both rat strains.     

Strain-related differences in bacterivory and demography of Diaphanosoma mongolianum (Cladocera) in relation to diet and previous exposure to cyanobacteria in nature

We compared the demographic variables and bacterivory of two strains of Diaphanosoma mongolianum from two water bodies in Spain, one without Microcystis (Maidevera in Zaragoza) and the other with dense Microcystis (La Albufera of Valencia). We hypothesized that the strain rarely exposed to Microcystis would be unable to grow on this cyanobacterial diet. We fed both strains Monoraphidium caribeum and Microcystis aeruginosa, together and separately, and compared their demographic variables. Monoraphidium caribeum was cultured in the laboratory on a defined medium, while the cyanobacteria were collected from La Albufera and sonicated before feeding the cladocerans (at 0.5?×?10⁶ cells ml^?1). We also tested the growth of D. mongolianum on bacterial diets by using seston (0–15 µm), bacterioplankton (0–3 µm) and mixed fractions (3–15 µm), from sieving Lake Albufera. We conducted population growth and life table demography experiments at 25 °C, using the two strains of D. mongolianum. Both strains had r (population growth rate) ranging from 0.05 to 0.3 d^?1, on all diets. The r was higher (0.18 d^?1) on the 0–15 µm seston compared to the mixed fraction (0.12 d^?1) although D. mongolianum also grew well on bacterioplankton (0.16 d^?1) alone. The response of the strains collected from two different water bodies was different to the test diets. We found that both strains of D. mongolianum could effectively utilize Microcystis for survival and growth, regardless of previous exposure to the cyanobacteria. The tested cladocerans could also grow well on small sized food particles (0–3 µm and 0–15 µm). Our results explain why D. mongolianum is common in eutrophic water bodies

     

New differences between the Wistar rat and Octodon degus, a putative laboratory animal resistant to morphine

1. The effects of CNS depressants (methadone and alcohol) and natural neurotransmitters (NA and ACh) are studied in O. degus. 2. O. degus shows resistance to methadone in the formalin algesiometric test and EEG. 3. Ethanol elimination profile suggest the presence of an atypical alcohol dehydrogenase in O. degus 4. O. degus is extremely resistant to the pressor effects of noradrenaline 5. the isolated atrium of this rodent is 40 times more sensitive to the negative chronotropic effect of methadone, than the rat atrium. 6. These effects could be explained in terms of an important catecholamine and endorphin co-secretion from adrenal glands in O. degus.     

Neuropathology and behavioral impairments in Wistar rats with a 6-OHDA lesion in the substantia nigra compacta and exposure to a static magnetic field

Studies have sought to assess various potential neuroprotective therapeutics in Parkinson's disease. The aim of this study was to evaluate the effects of static magnetic field stimulation 14 days after a 6-Hydroxydopamine (6-OHDA) substantia nigra compacta (SNc) lesion on motor behavior, as assessed by the rotarod (RR) test and brain tissue morphology. Forty male Wistar rats were used and were divided into five groups: control group, sham group (SG), lesion group (LG), lesion north pole group (LNPG) and lesion south pole group (LSPG). In groups with magnetic stimulation, a 3200-gauss magnet was fixed to the skull. After the experiments, the animals were anesthetized for brain perfusion. Coronal sections of the SNc were stained with Nissl. The RR test showed a decrease in the time spent on the apparatus in the LG compared with all groups. The LNPG and LSPG had significant increases in the time spent when compared to the LG. A morphometric analysis revealed a significant reduction in the number of neurons in the LG, LNPG and LSPG in relation to the SG. There were a higher number of neurons in the LNPG and LSPG than the LG, and a higher number of neurons in the LSPG than the LNPG. We observed that the LG, LNPG and LSPG showed a higher number of glial cells than the SG, and the LNPG and LSPG showed a lower number of glial cells than the LG. Our results demonstrate a potential therapeutic use of static magnetic fields for the preservation of motor behavior and brain morphology in the SNc after 14 days with 6-OHDA lesion.     

Spatial working memory in rats: no differences between the sexes

In a number of mammalian species, males appear to have superior spatial abilities to females. The favoured explanations for this cognitive difference are hormonal, with higher testosterone levels in males than females leading to better spatial performance, and evolutionary, where sexual selection has favoured males with increased spatial abilities for either better navigational skills in hunting or to enable an increased territory size. However, an alternative explanation for this sex difference focuses on the role of varying levels of oestrogen in females in spatial cognition (the 'fertility and parental care' hypothesis). One possibility is that varying oestrogen levels result in variation in spatial learning and memory so that, when tested across the oestrous cycle, females perform as well as males on days of low oestrogen but more poorly on days of high oestrogen. If day in the oestrous cycle is not taken into account then, across an experiment, any sex differences found would always produce male superiority. We used a spatial working memory task in a Morris water maze to test the spatial learning and memory abilities of male and female rats. The rats were tested across a number of consecutive days during which the females went through four oestrous cycles. We found no overall sex differences in latencies to reach a submerged platform in a Morris water maze but, on the day of oestrus (low oestrogen), females took an extra swim to learn the platform's location (a 100% increase over the other days in the cycle). Female swim speed also varied across the oestrous cycle but females were no less active on the day of oestrus. These results oppose the predictions of the fertility and parental care hypothesis.     

Oral astringency: effects of repeated exposure and interactions with sweeteners

The perceived dryness and bitterness associated with the astringentstimulus tannic acid were examined in a series of experiments.The method of magnitude estimation was used in conjunction witha sip and spit procedure to measure changes in these two oralsensations during repeated exposures to the test stimulus. Salivaryvolume was also measured. The results indicated (i) that mouthdryness increased significantly over time, whereas bitternessincreased only slightly over time, and (ii) the addition ofsweeteners to solutions of tannic acid reduced both perceiveddryness and bitterness. It was concluded that the attenuationof dryness by sweeteners was probably related to increases insalivary volume produced by the sweeteners, although the lubricatingcharacteristics of the viscous sucrose solutions may also haveplayed a role.