Sprague-Dawley Strain Research Articles

Maternal and genetic factors in stress-resilient and -vulnerable rats: A cross-fostering study

Early environmental factors can modulate the development of the hypothalamic–pituitary–adrenal (HPA) axis response to stress, together with subsequent brain functions and emotional behaviors. Two rat strains, Sprague–Dawley (SD) and Fischer 344 (F344), are known to exhibit differences in HPA axis reactivity and anxiety behavior in response to restraint stress in adulthood. To investigate the contribution of maternal influences in determining HPA axis and behavioral responses to stress, a cross-fostering study was performed using stress-resilient (SD) or stress-susceptible (F344) strains. We found that SD rats adopted by either an SD (in-fostered) or an F344 (cross-fostered) dam and F344 rats adopted by an SD dam (cross-fostered) showed a suppression of the HPA axis response following 14 days of repeated restraint stress. In contrast, F344 rats adopted by an F344 dam (in-fostered) did not show such HPA axis habituation. We also found that F344 rats adopted by an F344 dam showed increased anxiety-related behaviors in social interaction and novelty-suppressed feeding tests as a result of the 14 days of restraint stress, while SD rats adopted by either an SD or an F344 dam and F344 rats adopted by an SD dam showed normal anxiety-related behaviors under the same experimental conditions. These results suggest that while genetic differences between SD and F344 strains account for some of the variations in stress vulnerability, maternal factors also contribute.

Antidepressant-Like Effects of κ-Opioid Receptor Antagonists in Wistar Kyoto Rats

The Wistar Kyoto (WKY) rat strain is a putative genetic model of comorbid depression and anxiety. Previous research showing increased kappa-opioid receptor (KOR) gene expression in the brains of WKY rats, combined with studies implicating the KOR in animal models of depression and anxiety, suggests that alterations in the KOR system could have a role in the WKY behavioral phenotype. Here, the effects of KOR antagonists in the forced swim test (FST) were compared with the WKY and the Sprague-Dawley (SD) rat strains. As previously reported, WKY rats showed more immobility behavior than SD rats. The KOR antagonists selectively produced antidepressant-like effects in the WKY rats. By contrast, the antidepressant desipramine reduced immobility in both strains. Brain regions potentially underlying the strain-specific effects of KOR antagonists in the FST were identified using c-fos expression as a marker of neuronal activity. The KOR antagonist nor-binaltorphimine produced differential effects on the number of c-fos-positive profiles in the piriform cortex and nucleus accumbens shell between SD and WKY rats. The piriform cortex and nucleus accumbens also contained higher levels of KOR protein and dynorphin A peptide, respectively, in the WKY strain. In addition, local administration of nor-binaltorphimine directly into the piriform cortex produced antidepressant-like effects in WKY rats further implicating this region in the antidepressant-like response to KOR antagonists. These results support the use of the WKY rat as a model of affective disorders potentially involving KOR overactivity and provide more evidence that KOR antagonists could potentially be used as novel antidepressants.

Diazepam Metabolism in the Kidneys of Male and Female Rats of Various Strains

Previously, we have reported drastic strain differences of diazepam metabolism in the livers of a variety of rat strain. In this study, to characterize strain and sex differences of diazepam metabolism in the kidney, renal microsomal diazepam metabolic activities were determined in the Dark Agouti (DA), Sprague-Dawley (SD), Brown Norway (BN) and Wistar (WS) strains of rat. We found that the major pathway of diazepam metabolism in the kidney was diazepam N-demethylation, which is different from that in the liver, 3-hydroxylation. A Dose-course (12.5-200 muM of diazepam) study revealed that the DA and WS male rats had higher diazepam N-demethylation activity than the SD and BN rats. In contrast to the males, a lower activity of diazepam N-demethylation was observed in female BN rats. By Western blot analysis, constitutive protein expressions of cytochrome P450 (CYP) 2C11, which is responsible for diazepam N-demethylation, were detected in the 4 strain in both the male and female rats, and the BN rats had lower expression levels of CYP2C11 protein. However, we did not observe significant differences in the kinetic parameters of diazepam N-demethylation. Our results suggested that there was a strain difference in CYP-dependent diazepam N-demethylation in the rat kidney, which is different from the finding in liver microsomes.

EFFECT OF CYNARA SCOLYMUS L. (ARTICHOKE) EXTRACT ON LIPID PROFILE OF HYPERLIPIDEMIC MALE RATS

Introduction: Cynara scolymus L. (Artichoke) grows in Egypt and other countries. It is used as foods and has medicinal properties. Artichoke extracts have been shown to produce various pharmacological effects, such as the inhibition of cholesterol biosynthesis and low density lipoprotein (LDL) oxidation. Purpose: To study the effect of Cynara scolymus L. and its extract on lipid profile of hyperlipidemic male rats. Study Design: Eighty male albino rats, Sprague-Dawley strain, weighing (204.0±10) were housed individually in wire-mesh cages. Induction of hyperlipidemia was carried out on all rats except negative control group by addition of cholesterol to the basal diet (2%) +0.25 bile salts (taurocholic) for 4 weeks. After that the rats were divided into 8 groups (10 rats each), the first (1st) and 2nd groups was negative (normal) and positive control groups (hyperlipidemic), groups from G 3: G8, they were fed on basal diet supplemented with 2 level of extract (4 & 8 %) of either heads, heads, or leaves extract. At the end of the experimental period (6 weeks treatment) rats were fasted over night before sacrificing, blood was collected, centrifuged; serum or plasma was stored at - 20 0C until analysis. Lipid profile and triacylglycerol were measured. Results and Discussion: Artichoke extracts (plant, head, and leaves) significantly reduced cholesterol, low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C) and triacylglycerol. No change was observed with high density lipoprotein cholesterol (HDL-C). Heads extract being more powerful. This effect may be due to its content of mono- and di-caffeoylquinic acids, flavonoids and other contents or through inhibition of LDL oxidation. Conclusion: artichoke extract seems to be positively modulate hypercholesterolemia and can provide a protection from cardiovascular diseases.

Evaluation ofIn VitroCultured Rat Oocytes, from Different Strains, by Spindle Morphology and Maturation-Promoting-Factor Activity Combined with Nuclear-Transfer Experiments

Although successful nuclear transfer (NT) has been reported in the rat 6 years ago, somatic cell nuclear transfer (SCNT) in the rat could not be repeated. Our experiments with rat SCNT reveal the difficulties related to rat cloning. We first focussed on the most appropriate rat strain that could be used as an oocyte donor. Then we describe how rat oocytes can be kept in a nonactivated state during in vitro culture, because the latter undergo spontaneous partial activation through rapid extrusion of the second polar body after isolation from the oviduct. In the SCNT experiments performed with the one-step manipulation technique it was possible to produce rat embryos, which developed in vivo up to the blastocyst stage. In addition, we identified the implantation sites of SCNT rat embryos reconstructed with Sprague-Dawley (SD) oocytes. Furthermore, different rat strains were used as oocyte donors and their oocytes were cultured under different conditions to establish a stable nonactivating oocyte culture system. The ratio of activated to nonactivated oocytes was measured by spindle-stability and maturation promoting factor (MPF) activity. These measurements indicated that a substrain of the SD rat strain, the so-called OFA-SD strain, is the one providing the most stable oocytes, when their oocytes are cultured in the presence of the proteasome inhibitor MG132. However, it was not possible to obtain any implantation sites with reconstructed oocytes derived from the OFA-SD strain transferred to foster mothers. This goal was not achieved, even when the trichostatin A (TSA) treatment was used, which is known to enhance the cloning efficiency of reconstructed mouse, porcine, bovine, and rabbit oocytes both in vitro and in vivo by enhancing the reprogramming efficiency of the recipient nucleus.

Antidepressant-like activity of sodium ferulate measured by chronic experimental method in rat model of depression

Objective To measure the antidepressive activity of sodium ferulate (SF) in chronic unpre-dictable mild stress (CUMS) rat model of depression. Methods Male Sprague-Dawley (SD) strain rats weighing 220～280g were divided into six matched groups (n=11 in each group ) based on their sucrose consumption in preliminary tests (1% sucrose solution) : control, CUMS(model) , CUMS + fluoxetine (FLU) ( positive control), and treatment ( CUMS + SF) groups. The rats in model group were exposed to CUMS for 28 days;the rats in posi-ly) for 28 days;the animals in treatment groups were exposed to CUMS and received administration of SF (20,40, care and received ip administration of normal saline simultaneously. The rats except control were housed separately in different rooms during the duration of the stress procedure. The rat model of depression was established by expo-sing to an unpredictable sequence of stressors;the body weight,food intake and fluid consumption were measured ;the behaviors were examined by open field and forced-swimming tests. A representative sections cutting across hip-pocampal area of the rats in the six groups were examined by light microscopy. Results The rat model of depres-sion has been established successfully at 28th day. The results showed that chronic ip administration of SF signifi-cantly reversed the effects of CUMS on the body weight gain,the consumption of sucrose solution,the squares cross-ing and rearing in open field test and the immobility time during forced-swimming test of the rats [(88.06±7.83) g vs. (77.15±14.66 )g;(66.33±3.03)g vs. (40.75±6.05)g;(25.10±4,90) times vs. (18.20±2.00) times, (6.60±1.20 ) times vs. (3.20±0.60) times ;(117.30±7.22) s vs. (148.10±8.25)s], the values of P were 0.0425,0.0087,0.0409,0.0317,0.0025 respectively,and also partially reversed the effects of CUMS on his-topathology of hippoeampus. Conclusion SF possesses potent antidepressant-like activity,and the antidepressant-like action may result from its neuroprotective effect. Key words: Sodium ferulate; Anti-depressive activity; Chronic unpredictable mild stress; Animal models, Rat

Effects of lotus root and lotus leaf extracts on physical and sociopsychological stress in rats fed high fat diet

Lotus has been known to be effective in the lowering of hyperlipidemic levels. But, there have not been reports regarding the effects of lotus in lowering serum lipid levels under stress. The present study was designed to determine the possible effect of lotus root and leaf extracts on physical and sociopsychological stress in rats which were fed a high fat diet. The experiments were performed with the use of young (5 weeks of age) male rats of Sprague‐Dawley strain. The rats were fed with high fat diets and orally administered once a day 200 mg/kg body weight of lotus root extract for 8 weeks. Physical stress and sociopsychological stress were exposed by foot‐shock for 1 hour (10 sec duration at intervals of 60 sec) everyday for 3 weeks using a communication box. The rats were divided into seven groups: CON (without stress), FS (Foot‐shocked group), NFS (Nonfoot‐shocked group), FSR(Foot‐shocked with lotus root extracts), FSL (Foot‐shocked with lotus leaf extracts), NFSR (Nonfoot‐shocked with lotus root extracts) and NFSL (Nonfoot‐shocked with lotus leaf extracts). The final body weight of the rats in the groups of FS, FSR and FSL were lower compared to the CON group. Prolonged 3‐week physical stress resulted in reduced total body weight gains. Blood triglyceride and total‐cholesterol levels were decreased by physical stress and blood total‐cholesterol level was increased by sociopsychological stress. The lipid lowering effect was the most prominent in the FSL group. Blood lipid levels of the sociopsychological stress groups showed an increasing tendency when lotus root and lotus leaf extracts were administered. These results suggest that administration of lotus leaf extracts on physical stress was effective in reducing lipid levels in a high fat diet.

Transgenic Expression of Aflatoxin Aldehyde Reductase (AKR7A1) Modulates Aflatoxin B1 Metabolism but not Hepatic Carcinogenesis in the Rat

In both experimental animals and humans, aflatoxin B(1) (AFB(1)) is a potent hepatic toxin and carcinogen against which a variety of antioxidants and experimental or therapeutic drugs (e.g., oltipraz, related dithiolethiones, and various triterpenoids) protect from both acute toxicity and carcinogenesis. These agents induce several hepatic glutathione S-transferases (GST) as well as aldo-keto reductases (AKR) which are thought to contribute to protection. Studies were undertaken in transgenic rats to examine the role of one inducible enzyme, AKR7A1, for protection against acute and chronic actions of AFB(1) by enhancing detoxication of a reactive metabolite, AFB(1) dialdehyde, by reduction to alcohols. The AFB(1) dialdehyde forms adducts with protein amino groups by a Schiff base mechanism and these adducts have been theorized to be at least one cause of the acute toxicity of AFB(1) and to enhance carcinogenesis. A liver-specific AKR7A1 transgenic rat was constructed in the Sprague-Dawley strain and two lines, AKR7A1(Tg2) and AKR7A1(Tg5), were found to overexpress AKR7A1 by 18- and 8-fold, respectively. Rates of formation of AFB(1) alcohols, both in hepatic cytosols and as urinary excretion products, increased in the transgenic lines with AKR7A1(Tg2) being the highest. Neither line offered protection against acute AFB(1)-induced bile duct proliferation, a functional assessment of acute hepatotoxicity by AFB(1), nor did they protect against the formation of GST-P positive putative preneoplastic foci as a result of chronic exposure to AFB(1). These results imply that the prevention of protein adducts mediated by AKR are not critical to protection against AFB(1) tumorigenicity.

Amphetamine effects on startle gating in normal women and female rats

Dopamine agonists disrupt prepulse inhibition (PPI) of startle in male rodents. In humans, this is observed only in some studies. We reported that PPI was disrupted by D: -amphetamine in men, but only among those with high basal PPI levels. Here, amphetamine effects on PPI were tested in normal women and female rats. Acoustic startle and PPI were tested in normal women after placebo or 20 mg amphetamine, in a double-blind, crossover design, and in female rats after vehicle or 4.5 mg/kg amphetamine. Rats were from Sprague-Dawley (SD) and Long Evans (LE) strains that differ significantly in gene expression in PPI-regulatory circuitry, including levels of nucleus accumbens (NAC) catechol-O-methyl transferase (COMT) mRNA. Amphetamine was bioactive in humans based on quantitative autonomic and self-rating measures, but did not significantly change startle magnitude or PPI across all subjects. Amphetamine's effects on PPI in women correlated significantly (p < 0.0008) with placebo PPI levels (reducing PPI only in women whose basal PPI levels exceeded the sample median) and with measures of novelty and sensation seeking. Amphetamine decreased PPI in SD rats that have relatively low NAC COMT gene expression and increased PPI in LE rats that have relatively high NAC COMT gene expression. The dopaminergic regulation of PPI in humans is related to basal levels of sensorimotor gating and to specific personality traits in normal men and women. In rats, the effects of amphetamine on PPI differ significantly in strains with low vs. high NAC COMT expression.

Effect of two mushroom varieties intake on serum triglycerides, cholesterol fractions and serum glucose levels in Albino rats

Abstract The present investigation was carried out in an attempt to assess the effect of nutrition with the two studied mushroom varieties namely, (Agaricus bisporus) and (Pleurotus ostreatus) on triglycerides and cholesterol fractions levels in albino rats, namely: total cholesterol, HDL-cholesterol, LDL-cholesterol and glucose content in the blood serum of the experimental albino rats after feeding with the four studied mushroom varieties such 10% (Agaricus bisporus), 10% (Pleurotus ostreatus), 5% (Agaricus bisporus)and 5% (Pleurotus ostreatus). The experiment included (56) males white albino rats (Sprague dawley strain) weighing between (100 – 120 g) divided into 6 groups with every group included 6 rats. Rats were housed individually in wire cages under the normal laboratory conditions and fed on the basal diet for a week as adaptation period. Daily administrations were continued for two successive periods (6) weeks each. In the first period one group was used as control and was fed on basal diet, including casein (12.5%), corn oil (10%), vitamin mixture (1%), salt mixture (3.5%), cellulose (5%), choline chloride (0.2%) and corn starch (67.8%). While, the other five groups were fed hyperlipidemic diet including (basal diet supplemented by 10% animal fat excluding 10% corn plus 1% cholesterol). In the second period, one group of hyperlipidiemic rats was fed on hyperlipidemic diet supplemented with different levels of the two studied mushroom varieties (Agaricus bisporus) and (Pleurotus ostreatus). Blood samples were collected from the retro-orbital sinus under rat eye in a clean sterile centrifuge tube by the end of the experiment. Samples were tightly kept in a sealed aliquot tube at -20oC until biochemical assays. There were significant differences between untreated group and all other (5) studied groups of the experimental rats (P < 0.05) in the serum triglycerides, total cholesterol, HDL cholesterol, LDL cholesterol, VLDL cholesterol and serum glucose levels, while group (3) (treated group fed on hyperlipidemic diet plus 10% Agaricus bisporus) recorded the lowest mean. Key Words: Mushrooms (Agaricus bisporus), (Pleurotus ostreatus), triglycerides, cholesterol, hyperlipidemic and glucose.

Effects of natural point mutation of rat aquaporin 5 expressed in vitro on its capacity of water permeability and membrane trafficking

In the colony of Sprague-Dawley (SD) strain, we found that there were rats expressing a mutant AQP5, which has a point mutation at nt 308 (G308A), leading to a replacement of (103)Gly with (103)Asp in the 3rd transmembrane domain. The mutant molecule scarcely expressed in the acinar cells, probably because of ineffective trafficking. The mutant molecule, however, showed normal water permeability when assessed by the oocyte system.

Effects of 12 Weeks of Exercise on Hepatic TNF-α and PPARα in an Animal Model of High-Fat Diet-Induced Nonalcoholic Steatohepatitis

Nonalcoholic steatohepatitis (NASH) is hepatic inflammation caused by a buildup of fat in the liver. This study was designed to examine whether the NASH-associated increase in hepatic TNF-α mRNA expression and serum TNF-α, and decrease in hepatic PPARα mRNA expression in rats secondary to 12-week consumption of a high-fat diet would be attenuated with concurrent exercise. A total of 28 male Sprague-Dawley strain rats were randomly assigned into four groups: standard diet without (C, n = 6) and with (E, n = 7) concurrent exercise; and high-fat diet without (H, n = 8) and with (HE, n = 7) concurrent exercise. The mean daily energy intake during the intervention period resulting from the standard and high-fat diets was approximately 82 kcal and 95 kcal, respectively. Swimming exercise was carried out in the E and HE groups for 12 weeks. The initial swimming duration of 30 minutes was progressively increased by 10 min·d −1 to 90 minutes by the end of the fourth week, which then remained unchanged. NASH revealed by histological activity index, which occurred in the H but not the C group, was alleviated in the HE group. Moreover, the upregulation of hepatic TNF-α mRNA expression and serum TNF-α, and downregulation of hepatic PPARα mRNA expression, which were shown in the H group, were attenuated in the HE group. Such findings suggest that long-term exercise carried out concurrently with consumption of a high-fat diet could alleviate high-fat diet-induced NASH. These may be partly attributable to the attenuation of hepatic TNF-α overexpression and the upregulation of hepatic PPARα mRNA expression.

Life History of Cones in the Rhodopsin-Mutant P23H-3 Rat: Evidence of Long-term Survival

To follow the status of cones over the life of the P23H-3 transgenic rat, while the rod population is depleted. P23H-3 heterozygous and Sprague-Dawley (SD) control rats were raised in dim, cyclic light from postnatal day (P)10 to P540. Retinas were examined for cone density, cone outer segment (OS) length, cone axon and soma morphology, and the amplitude of rod and cone components of the electroretinogram (ERG) were determined. In the P23H-3 retina, cone density followed a developmental pattern, increasing from P10 until P20, declining during early adult life (to P150), then steadying at levels found in the SD retina until P540. Cone OSs elongated to P30 and then slowly shortened during late adulthood; at P350 and P540, cone OSs were significantly shorter than in the background SD strain. Cone axons shortened slowly throughout adult life as the outer nuclear layer thinned. The rod a-wave declined steadily in the P23H-3 retina from P10, falling below amplitudes seen in the SD strain from early life. By contrast, the cone b-wave maintained amplitude at SD levels, until P380. Despite the ongoing loss of rod function and numbers, cone numbers in the P23H-3 retina were maintained at levels found in the SD rat to the oldest age examined, and cone function and OS morphology were maintained for approximately 1 year, indicating a long period of cone independence. The long period of cone survival creates an opportunity to induce self-repair, if the stress causing their dysfunction can be reduced.

Heritable strain differences in sensitivity to the startle gating-disruptive effects of D2 but not D3 receptor stimulation

Prepulse inhibition (PPI) of the startle reflex is an operational measure of sensorimotor gating that is deficient in several brain disorders and is disrupted in rats by dopamine (DA) agonists. Robust heritable strain differences are observed between Sprague-Dawley (SD) and Long-Evans (LE) strains in sensitivity to the PPI-disruptive effects of DA agonists associated with differential gene expression in the nucleus accumbens. Here, we compared the contribution of D2 versus D3 receptors with this heritable difference, using the D3-preferential agonist (pramipexole), the mixed D3/D2 agonist (quinpirole), the mixed D1/D2-like agonist (apomorphine), and the preferential D2 antagonist (L741,626). All DA agonists disrupted PPI in SD and LE rats. Greater sensitivity for this effect was evident with apomorphine and quinpirole in SD than LE rats, but not with pramipexole. The selective D2 antagonist L741,626 preferentially reversed apomorphine-induced PPI deficits at a dose that did not alter pramipexole-induced PPI deficits. We conclude that the heritable pattern of greater PPI 'disruptability' by DA agonists in SD versus LE rats reflects differences in D2 but not D3 receptor-associated mechanisms.

Effects of dietary ascorbic acid supplementation on lipid peroxidation and the lipid content in the liver and serum of magnesium-deficient rats.

We investigated the effects of ascorbic acid (AsA) supplementation on lipid peroxidation and the lipid content in the liver and serum of magnesium (Mg)-deficient rats. Eighteen 3-week-old male Sprague-Dawley strain rats were divided into 3 groups and maintained on a control diet (C group), a low-Mg diet (D group), or a low-Mg diet supplemented with AsA (DA group) for 42 d. At the end of this period, the final body weight, weight gain, and serum Mg concentrations were significantly decreased in the Mg-deficient rats. Further, dietary AsA supplementation had no effect on the growth, serum Mg concentration, Mg absorption, and Mg retention. The serum concentration of AsA was significantly lower in the D group than in the C group but was unaltered in the DA group. The levels of phosphatidylcholine hydroperoxide (PCOOH) in the serum and of triglycerides (TGs) and total cholesterol (TC) in the serum and liver were significantly higher in the D group than in the C group. The serum PCOOH, liver TG, and liver TC levels were decreased in the DA group. These results indicate that Mg deficiency increases the AsA requirement of the body and that AsA supplementation normalizes the serum levels of PCOOH and the liver lipid content in Mg-deficient rats, without altering the Mg status.

An in vivo rat model for early development of colorectal cancer metastasis to liver

At diagnosis of colorectal cancer, approximately 25% of the patients have established colorectal liver metastasis. Optimal management of disseminated disease requires therapies targeting multiple stages in hepatic colorectal cancer metastasis development. To facilitate this, biologically accurate in vivo models are required. Early colonic cancer liver metastases development was studied using BDIX and Sprague-Dawley rat strains with human HT29 and rat DHDK12 colonic cancer cell lines. Different cancer cell-host combinations were used. Rat DHDK12 was previously chemically induced in the BDIX rat. Real-time intra-vital microscopy was employed to analyse the early development of liver metastases in four groups (n = 6 per group) (HT29-BDIX, DHDK12-BDIX, HT29-SD and DHDK12-SD). Data were compared using one-way anova with Bonferroni's multiple comparison test. The total number of tumour cells visualized, adherent cells within the hepatic sinusoids, extravasated tumour cells and migration rates were significantly higher in the DHDK12-BDIX combination. Maximum number of visualized cells and maximum migration rate were also significantly higher in this group. No significant differences were observed in these experimental parameters among the other three groups or in the haemodynamic parameters among all groups. In conclusion, cancer cell line-host selection has a significant effect on early colonic cancer liver metastasis development.

Vasopressin-stimulated Increase in Phosphorylation at Ser269 Potentiates Plasma Membrane Retention of Aquaporin-2

Vasopressin controls water excretion through regulation of aquaporin-2 (AQP2) trafficking in renal collecting duct cells. Using mass spectrometry, we previously demonstrated four phosphorylated serines (Ser256, Ser261, Ser264, and Ser269) in the carboxyl-terminal tail of rat AQP2. Here, we used phospho-specific antibodies and protein mass spectrometry to investigate the roles of vasopressin and cyclic AMP in the regulation of phosphorylation at Ser269 and addressed the role of this site in AQP2 trafficking. The V2 receptor-specific vasopressin analog dDAVP increased Ser(P)269-AQP2 abundance more than 10-fold, but at a rate much slower than the corresponding increase in Ser256 phosphorylation. Vasopressin-mediated changes in phosphorylation at both sites were mimicked by cAMP addition and inhibited by protein kinase A (PKA) antagonists. In vitro kinase assays, however, demonstrated that PKA phosphorylates Ser256, but not Ser269. Phosphorylation of AQP2 at Ser269 did not occur when Ser256 was replaced by an unphosphorylatable amino acid, as seen in both S256L-AQP2 mutant mice and in Madin-Darby canine kidney cells expressing an S256A mutant, suggesting that Ser269 phosphorylation depends upon prior phosphorylation at Ser256. Immunogold electron microscopy localized Ser(P)269-AQP2 solely in the apical plasma membrane of rat collecting duct cells, in contrast to the other three phospho-forms (found in both apical plasma membrane and intracellular vesicles). Madin-Darby canine kidney cells expressing an S269D "phosphomimic" AQP2 mutant showed constitutive localization at the plasma membrane. The data support a model in which vasopressin-mediated phosphorylation of AQP2 at Ser269:(a) depends on prior PKA-mediated phosphorylation of Ser256 and (b) enhances apical plasma membrane retention of AQP2.

Comparison of the behavioural pharmacology of the Lister-Hooded with 2 commonly utilised albino rat strains

The use of animal models (particularly rats) in research for developing drugs for central nervous system diseases is well validated. However a range of strains are often utilised in these models. The Lister-Hooded (LH) strain is beginning to be increasingly used in preclinical investigations. Thus, the objective of the present study was to investigate the comparative behavioural pharmacology of this strain, with the two most widely used rat strains, namely the Sprague–Dawley (SD), and Wistar (W) strains. The tests used were the forced swim test (FST) for antidepressants, the amphetamine-locomotor activity test for antipsychotics, the elevated plus maze (EPM) for anxiolytics, as well as tests of general locomotor activity using home cage monitoring (HCM) and the open field test. Continuous HCM revealed a significantly higher daily activity and lower nocturnal activity for LH compared to the other strains; there were no strain-related differences in the open field test. In the FST, there were no strain differences in immobility time and a similar magnitude of desipramine-induced reduction in immobility across strains. In the locomotor activity test, control LH rats showed significantly higher activity whilst significant amphetamine-induced hyperactivity was seen only with the LH and W strains. In the EPM, control LH rats had a significantly larger percentage of open arm entries, whilst only the SD strain displayed a significant diazepam-induced increase in this parameter. These findings suggest that strain variation can cause markedly different results in behavioural pharmacological tests where locomotor activity plays a significant role, and should be taken into account when selecting a strain for evaluating the behavioural effects of psychotropic drugs. Such differences in locomotor activity in the LH strain could be accounted for by an altered diurnal pattern in this strain.

Studies of Various Biochemical Parameters of Rat Plasma Following Chronic Administration of “Rohitakarista”-An Ayurvedic Formulation

The study was carried out to investigate the safety profile as well as the effect of "Rohitakarista" (RHT) on various biochemical parameters of rats' plasma after chronic administration. RHT, a classical Ayurvedic preparation used in hepatosplenic disorders, was administered per oral route at a dose of 100 mg kg(-1) body weight, once daily, up to 46 days for all the experiments. Forty albino rats (Rattus novergicus: Sprague-Dawley strains), equally of both sexes, were randomly grouped into four where each group had ten animal/sex. One male and one female group were used as control and other groups were used as test. In the male, rats there was a statistically insignificant increase (p = 0.763) in the total protein but there was a statistically significant increase (p = 0.022) in the total protein content of the plasma of female rats. Statistically very high significant increase (male: p = 0.001 and female: p = 0.001) in the albumin content of the plasma was noted in both sexes. In case of bilirubin, interestingly it was decreased very high significantly (p = 0.001) in plasma of male rats but increased very high significantly (p = 0.001) in the plasma of female rats. In the male rats, statistically there was a very high significant decrease (sGPT: p = 0.001, sGOT: p = 0.001 and ALP: p = 0.001) in the sGPT, sGOT and ALP activities in the plasma. On the other hand, statistically there was a very highly significant increase (sGPT: p = 0.001, sGOT: p = 0.001 and ALP: p = 0.001) in the sGPT, sGOT and ALP activities in the plasma of female rats. Very high significant decrease (male: p = 0.001 and female: p = 0.001) in creatinine in plasma of both sexes were observed after chronic administration of RHT. Urea in the plasma was decreased very high significantly (p = 0.001) in plasma of male rats but increased very high significantly (p = 0.001) in the plasma of female rats. There was high significant increase (p = 0.002) in uric acid in male rats. On the contrary, no significant increase (p = 0.324) of uric acid was observed in female rats.

The effects of light cycle phase on morphine-induced conditioned taste aversions in the Lewis, Fischer and Sprague-Dawley rat strains

The present experiment investigated the effect of light cycle phase on morphine-induced conditioned taste aversions in the Lewis (LEW), Fischer (F344) and Sprague-Dawley (SD) rat strains. Separate groups of rats from each strain were trained during either the light phase or the dark phase on a procedure in which saccharin was paired with one of two doses of morphine (or vehicle). With 3.2mg/kg morphine, strain differences were observed during the light phase, with F344 rats displaying a significantly stronger taste aversion than the LEW rats, who displayed a significantly stronger aversion than the SD rats. In contrast, during the dark phase, 3.2mg/kg morphine produced comparable, moderately strong aversions in all strains. With 10.0mg/kg morphine, F344 rats developed stronger aversions than either the LEW or SD rats in both phases of the light cycle. The effect of light cycle was most clearly seen in the SD rats, where stronger aversions were produced in the dark phase for both morphine doses. For the LEW rats, stronger aversions were produced in the dark as compared to the light only with the low dose of morphine. For the F344 rats, aversions of comparable strength were observed in both phases of the light cycle for both morphine doses. The finding that light cycle differentially affects morphine-induced taste aversions in these strains is consistent with what is known about strain differences in circadian patterns of corticosterone activity and with previous results relating corticosterone to morphine-induced taste aversions.