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Sample records for adult long-evans rats

  1. Structural and functional alterations of spinal cord axons in adult Long Evans Shaker (LES) dysmyelinated rats.

    PubMed

    Eftekharpour, Eftekhar; Karimi-Abdolrezaee, Soheila; Sinha, Kusum; Velumian, Alexander A; Kwiecien, Jacek M; Fehlings, Michael G

    2005-06-01

    Abnormal formation or loss of myelin is a distinguishing feature of many neurological disorders and contributes to the pathobiology of neurotrauma. In this study we characterize the functional and molecular changes in CNS white matter in Long Evans Shaker (LES) rats. These rats have a spontaneous mutation of the gene encoding myelin basic protein which results in severe dysmyelination of the central nervous system (CNS), providing a unique model for demyelinating/dysmyelinating disorders. To date, the functional and molecular changes in CNS white matter in this model are not well understood. We have used in vivo somatosensory evoked potential (SSEP), in vitro compound action potential (CAP) recording in isolated dorsal columns, confocal immunohistochemistry, Western blotting and real-time PCR to examine the electrophysiological, molecular and cellular changes in spinal cord white matter in LES rats. We observed that dysmyelination is associated with dispersed labeling of Kv1.1 and Kv1.2 K+ channel subunits, as well as Caspr, a protein normally confined to paranodes, along the LES rat spinal cord axons. Abnormal electrophysiological properties including attenuation of CAP amplitude and conduction velocity, high frequency conduction failure and enhanced sensitivity to K+ channel blockers 4-aminopyridine and dendrotoxin-I were observed in spinal cord axons from LES rats. Our results in LES rats clarify some of the key molecular, cellular and functional consequences of dysmyelination and myelin-axon interactions. Further understanding of these issues in this model could provide critical insights for neurological disorders characterized by demyelination. PMID:15869936

  2. Thermoregulatory deficits in adult Long Evans rat exposed perinatally to the antithyroidal drug, propylthiouracil.

    PubMed

    Johnstone, Andrew F M; Gilbert, Mary E; Aydin, Cenk; Grace, Curtis E; Hasegawa, Masashi; Gordon, Christopher J

    2013-01-01

    Developmental exposure to endocrine disrupting drugs and environmental toxicants has been shown to alter a variety of physiological processes in mature offspring. Body (core) temperature (T(c)) is a tightly regulated homeostatic system but is susceptible to disruptors of the hypothalamic pituitary thyroid (HPT) axis. We hypothesized that thermoregulation would be disrupted in adult offspring exposed perinatally to an HPT disruptor. Propylythiouracil (PTU) was used as a prototypical compound because of its well known antithyroidal properties. PTU was added to the drinking water of pregnant rats in concentrations of 0, 1, 2, 3, and 10 ppm from gestational day (GD) 6 through postnatal day (PND) 21. Adult male offspring were implanted with radiotransmitters to monitor Tc and motor activity (MA) and were observed undisturbed at an ambient temperature of 22 °C for 12 consecutive days. Data were averaged into a single 24 hour period to minimize impact of ultradian changes in T(c) and MA. All treatment groups showed a distinct circadian temperature rhythm. Rats exposed to 10 ppm PTU exhibited a marked deviation in their regulated T(c) with a reduction of approximately 0.4 °C below that of controls throughout the daytime period and a smaller reduction at night. Rats exposed to 1 or 2 ppm also had smaller but significant reductions in T(c). MA was unaffected by PTU. Overall, developmental exposure to moderate doses of an antithyroidal drug led to an apparent permanent reduction in T(c) of adult offspring that was independent of changes in MA. PMID:23732561

  3. In vivo cerebral incorporation of radiolabeled fatty acids after acute unilateral orbital enucleation in adult hooded Long-Evans rats

    SciTech Connect

    Wakabayashi, S.; Freed, L.M.; Bell, J.M.; Rapoport, S.I.

    1994-03-01

    We examined effects of acute unilateral enucleation on incorporation from blood of intravenously injected unsaturated [1-{sup 14}C]arachidonic acid ([{sup 14}C]AA) and [1-{sup 14}C]docosahexaenoic acid ([{sup 14}C]DHA), and of saturated [9,10-{sup 3}H]palmitic acid ([{sup 3}H]PA), into visual and nonvisual brain areas of awake adult Long-Evans hooded rats. Regional cerebral metabolic rate for glucose (rCMR{sub glc}) values also were assessed with 2-deoxy-D-[1-{sup 14}C]glucose ([{sup 14}C]DG). One day after unilateral enucleation, an awake rat was placed in a brightly lit visual stimulation box with black and white striped walls, and a radiolabeled fatty acid was infused for 5 min or [{sup 14}C]DG was injected as a bolus. [{sup 14}C]DG also was injected in a group of rats kept in the dark for 4 h. Fifteen minutes after starting an infusion of a radiolabeled fatty acid, or 45 min after injecting [{sup 14}C]DG, the rat was killed and the brain was prepared for quantitative autoradiography. Incorporation coefficients k* of fatty acids, or rCMR{sub glc} values, were calculated in homologous brain regions contralateral and ipsilateral to enucleation. As compared with ipsilateral regions, rCMR{sub glc} was reduced significantly (by as much as -39%) in contralateral visual areas, including the superior colliculus, lateral geniculate body, and layers I, IV, and V of the primary (striate) and secondary (association, extrastriate) visual cortices. These results indicate that enucleation acutely reduces neuronal activity in contralateral visual areas of the awake rat and that the reductions are coupled to reduced incorporation of unsaturated fatty acids into sn-2 regions of phosphatidylcholine, phosphatidylinositol, and phosphatidylethanolamine. Reduced fatty acid incorporation likely reflects reduced activity of phospholipases A{sub 2} and/or phospholipase C. 65 refs., 5 figs., 5 tabs.

  4. Skin tumors in aging Long Evans rats.

    PubMed

    Esfandiari, Adeleh; Loya, Theresa; Lee, Jeffrey L

    2002-06-01

    We report 25 cases of skin neoplasm observed among 30 Long Evans rats serving as controls in a psychosocial behavioral study conducted in the Vivarium at Charles R. Drew University, Los Angeles, CA. The animals were 10 weeks old at the beginning of the study. All the skin tumors developed at 18 to 26 months of age and slowly enlarged over a period of 9 months. Multiple nodules occurred in 8 males and 6 females. None of the tumors regressed. The tumors were located around the hind leg and dorso-medial area and measured 1 to 2 cm. Physical examination revealed firm well demarcated dermal masses. Most of the tumor nodules were intradermal, and some had a central ulcerated or keratin-filled core. Microscopic examination performed on some of the tumors showed findings of classic Keratoacanthoma, whereas others showed histologic features suggestive of squamous cell carcinoma. These findings indicate a high rate (83%) of spontaneous skin neoplasms among aging Long Evans rats. To our knowledge, such a high rate of skin neoplasms in aged rodents has not been described in the literature. Furthermore, further studies should be undertaken to confirm these findings and to assess whether these rodents might serve as a model for studying the alterations in the immune system with aging.

  5. Struvite Urolithiasis in Long-Evans Rats.

    PubMed

    Pang, Jassia; Borjeson, Tiffany M; Parry, Nicola M A; Fox, James G

    2015-12-01

    Struvite urinary calculi, which are composed of magnesium, ammonium, and phosphate, can cause complications including sepsis and renal failure. Struvite calculi were identified within the urinary bladder and renal pelvis of 2 Long-Evans rats that died within days after arrival from a commercial vendor. The remaining rats in the shipment were screened by physical examination, radiography, and ultrasonography, revealing an additional 2 animals that were clinically affected. These rats were euthanized, necropsied, and yielded similar findings to those from the first 2 rats. In addition, urine samples had an alkaline pH and contained numerous bacteria (predominantly Proteus mirabilis), leukocytes, and crystals. All calculi were composed completely of struvite. Another 7 rats in the shipment had alkaline urine with the presence of blood cells; 6 of these rats also had abundant struvite crystals, and P. mirabilis was cultured from the urine of 3 rats. Further investigation by the vendor identified 2 of 100 rats with struvite calculi from the same colony. Although no specific cause could be implicated, the fact that all the affected rats came from the same breeding area suggests a genetic or environmental triggering event; a contribution due to diet cannot be ruled out. Our findings suggest that the affected rats had metabolic disturbances coupled with bacterial infection that predisposed them to develop struvite calculi. During sudden increases of struvite urinary calculi cases in rats, urine cultures followed by appropriate surgical intervention and antibiotic therapy is warranted. Additional factors, including diet, merit attention as well. PMID:26678365

  6. Maternal Environmental Contribution to Adult Sensitivity and Resistance to Obesity in Long Evans Rats

    PubMed Central

    Schroeder, Mariana; Shbiro, Liat; Moran, Timothy H.; Weller, Aron

    2010-01-01

    Background The OLETF rat is an animal model of early onset hyperphagia induced obesity, presenting multiple pre-obese characteristics during the suckling period. In the present study, we used a cross-fostering strategy to assess whether interactions with obese dams in the postnatal environment contributed to the development of obesity. Methodology On postnatal Day (PND)-1 OLETF and control LETO pups were cross-fostered to same or opposite strain dams. An independent ingestion test was performed on PND11 and a nursing test on PND18. Rats were sacrificed at weaning or on PND90, and plasma leptin, insulin, cholesterol, triglycerides and alanine aminotransferase (ALT) were assayed. Fat pads were collected and weighed and adipocyte size and number were estimated. Body weight and intake, as well as the estrous cycle of the female offspring were monitored. Principal Findings During the suckling period, the pups' phenotype was almost completely determined by the strain of the mother. However, pups independently ingested food according to their genotype, regardless of their actual phenotype. At adulthood, cross fostered males of both strains and LETO females were affected in regard of their adiposity levels in the direction of the foster dam. On the other hand, OLETF females showed almost no alterations in adiposity but were affected by the strain of the dams in parameters related to the metabolic syndrome. Thus, OLETF females showed reduced liver adiposity and circulating levels of ALT, while LETO females presented a disrupted estrous cycle and increased cholesterol and triglycerides in the long term. Conclusions The present study provides further support for the early postnatal environment playing a sex-divergent role in programming later life phenotype. In addition, it plays a more central role in determining the functioning of mechanisms involved in energy balance that may provide protection from or sensitivity to later life obesity and pathologies related to the

  7. Chronic ethanol exposure increases voluntary home cage intake in adult male, but not female, Long-Evans rats.

    PubMed

    Morales, Melissa; McGinnis, Molly M; McCool, Brian A

    2015-12-01

    The current experiment examined the effects of 10 days of chronic intermittent ethanol (CIE) exposure on anxiety-like behavior and home cage ethanol intake using a 20% intermittent access (M, W, F) paradigm in male and female Long-Evans rats. Withdrawal from alcohol dependence contributes to relapse in humans and increases in anxiety-like behavior and voluntary ethanol consumption in preclinical models. Our laboratory has shown that 10 days of CIE exposure produces both behavioral and neurophysiological alterations associated with withdrawal in male rats; however, we have yet to examine the effects of this exposure regime on ethanol intake in females. During baseline, females consumed more ethanol than males but, unlike males, did not show escalations in intake. Rats were then exposed to CIE and were again given intermittent access to 20% ethanol. CIE males increased their intake compared to baseline, whereas air-exposed males did not. Ethanol intake in females was unaffected by CIE exposure. Notably, both sexes expressed significantly elevated withdrawal-associated anxiety-like behavior in the plus maze. Finally, rats were injected with the cannabinoid CB1 receptor antagonist, SR141716A (0, 1, 3, 10mg/kg, i.p.) which reduced ethanol intake in both sexes. However, females appear to be more sensitive to lower doses of this CB1 receptor antagonist. Our results show that females consume more ethanol than males; however, they did not escalate their intake using the intermittent access paradigm. Unlike males, CIE exposure had no effect on drinking in females. It is possible that females may be less sensitive than males to ethanol-induced increases in drinking after a short CIE exposure. Lastly, our results demonstrate that males and females may have different pharmacological sensitivities to CB1 receptor blockade on ethanol intake, at least under the current conditions.

  8. Adolescent social instability stress increases aggression in a food competition task in adult male Long-Evans rats.

    PubMed

    Cumming, Mark J; Thompson, Madison A; McCormick, Cheryl M

    2014-11-01

    Adolescent social instability stress (SS; daily 1 hr isolation + new cage partners postnatal days 30-45; thereafter with original cage partner, also in the SS condition) and control (CTL) rats competed for access to a preferred food in five sessions against their cage partner. In the first session, SS pairs displayed more aggression (face whacks, p = .02; rear attacks, p = .03), were less likely to relinquish access to the food voluntarily (p = .03), spent more time at the feeder than CTL pairs (p = .06), but did not differ in latency to access the feeder (p = .41). Pairs were considered in dominant-submissive relationships (DSR) if one rat spent significantly more time at the feeder than the other; 8 of 12 SS and 8 of 12 CTL pairs displayed DSRs (remaining: no-DSR). Aggression increased from the 1st to 5th session (p < .001), was greater in no-DSR than DSR pairs (p = .04; consistent with the proposed function of DSRs to be the reduction of aggression in groups), and was higher in SS than CTL pairs (p = .05). Because the increased aggression of SS compared with CTL pairs did not result in a significant increase in their time at the feeder, the increased aggression may be considered maladaptive, and may reflect an increased motivation for food reward. These results add to evidence that SS in adolescence modifies the adult social repertoire of rats and highlight the importance of adolescent social experiences for adult behavior.

  9. Breeder and batch-dependent variability in the acquisition and performance of a motor skill in adult Long-Evans rats.

    PubMed

    O'Bryant, Amber J; Allred, Rachel P; Maldonado, Monica A; Cormack, Lawrence K; Jones, Theresa A

    2011-10-10

    Reaching tasks are popular tools for investigating the neural mechanisms of motor skill learning and recovery from brain damage in rodents, but there is considerable unexplained variability across studies using these tasks. We investigated whether breeder, batch effects, experimenter, time of year, weight and other factors contribute to differences in the acquisition and performance of a skilled reaching task, the single pellet retrieval task, in adult male Long-Evans hooded rats. First, we retrospectively analyzed task acquisition and performance in rats from different breeding colonies that were used in several studies spanning a 3 year period in our laboratory. Second, we compared reaching variables in age-matched rats from different breeders that were trained together as a batch by the same experimenters. All rats had received daily training on the reaching task until they reached a criterion of successful reaches per attempt. We found significant breeder-dependent differences in learning rate and final performance level. This was found even when age-matched rats from different breeders were trained together by the same experimenters. There was also significant batch-to-batch variability within rats from the same breeder trained by the same experimenter. Other factors, including weight, paw preference and the experimenter, were not as strong or consistent in their contributions to differences across studies. The breeder and batch effects found within the same rat strain may reflect genetic and environmental influences on the neural substrates of motor skill learning. This is an important consideration when comparing baseline performance across studies and for controlling variability within studies.

  10. Predatory Odor Disrupts Social Novelty Preference in Long-Evans Rats

    ERIC Educational Resources Information Center

    Anderson, Matthew J.; Layton, William B.

    2012-01-01

    The present study examined the effects of predatory odor (cat urine) on social novelty preference in Long-Evans rats. Adult male subjects encountered a juvenile conspecific at training, were exposed to either clean cat litter (control) or litter soiled with cat urine (predatory odor), and were tested for social novelty preference. While the…

  11. Mammary gland development and response to prenatal atrazine exposure in the Sprague Dawley and Long-Evans rats.

    EPA Science Inventory

    Mammary gland (MG) tumor development in Sprague Dawley (SD) rats is increased by longterm dietary exposure to the chlorotriazine herbicide atrazine (ATR). ATR is proposed to cause these changes in the adult SD rat by altering hormonally-regulated estrous cyclicity. In Long-Evans...

  12. ADVERSE EFFECTS OF TCDD ON MAMMARY GLAND DEVELOPMENT IN LONG EVANS RATS: A TWO GENERATIONAL STUDY

    EPA Science Inventory

    Recent studies have demonstrated variable effects on mammary gland development in rat offspring exposed to TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin, 1 ug/kg, gavage) on day 15 of gestation. We have characterized these effects in Long Evans rats, in both one and two-generational...

  13. DEVELOPMENTAL EFFECTS OF TRICHLOROACETONITRILE ADMINISTERED IN CORN OIL TO PREGNANT LONG-EVANS RATS

    EPA Science Inventory

    Trichloroacetonitrile (TCAN) is a by-product of the chlorine disinfection of water containing natural organic material. When administered by gavage to pregnant Long-Evans rats in a medium-chain triglyceride vehicle, tricaprylin oil (Tricap), at a volume of 10 ml/kg, TCAN induced ...

  14. EVALUATION OF SENSORY EVOKED POTENTIALS IN LONG EVANS RATS GESTATIONALLY EXPOSED TO MERCURY (HGO) VAPOR.

    EPA Science Inventory

    Human exposure to mercury vapor (Hg0) has been reported to result in sensory disturbances. Developmental exposure to toxicants may result in long-lasting changes in neural function. This manuscript describes the lack of effect of gestational exposure of Long Evans rats to Hg0 on ...

  15. EVALUATION OF FERTILIZATION FOLLOWING OVULATORY DELAY WITH THIRAM IN THE LONG-EVANS HOODED RAT

    EPA Science Inventory

    Evaluation of fertilization following ovulatory delay with thiram in the Long-Evans Hooded Rat

    1TE Stoker, 1* S Jeffay, and 1 SD Perreault.

    1Gamete and Early Embryogenesis Biology Branch and 2 Endocrinology Branch, Reproductive Toxicology Division, NHEERL, US EPA, R...

  16. POSTNATAL DISPOSITION OF TCDD IN LONG EVANS RATS FOLLOWING GESTATIONAL EXPOSURE

    EPA Science Inventory

    POSTNATAL DISPOSITION OF TCDD IN LONG EVANS RATS FOLLOWING GESTATIONAL EXPOSURE.
    J J Diliberto', J T Hamm'.2, F McQuaid', and L S Birnbaum'. 'US EPA, ORD/NHEERL/ETD, RTP, NC; 2Curriculum in Toxicology, University of North Carolina, Chapel Hill, NC.
    2,3,7,8-Tetrachlorodibenz...

  17. BROMATE-INDUCED TRANSCRIPTIONAL CHANGES IN LONG-EVANS RAT KIDNEYS

    EPA Science Inventory


    Bromate-Induced Transcriptional Changes in Long-Evans Rat Kidneys.

    Ozone disinfection of surface waters containing bromide ion (Br-) results in the oxidation of bromide to bromate, which can be found in finished drinking water as a by-product. Potassium bromate (KBrO3)...

  18. ATRAZINE DISPOSITION IN PREGNANT AND LACTATING LONG-EVANS RATS

    EPA Science Inventory

    Atrazine (ATR) is a widely used herbicide shown to delay early mammary development in female offspring of gestationally exposed rats. The effects of ATR can be induced by in utero exposure and/or suckling from a dam exposed during late pregnancy, but ATR is reported to have a hal...

  19. Developmental Exposure to Polychlorinated Biphenyls Reduces Amphetamine Behavioral Sensitization in Long-Evans Rats

    PubMed Central

    Poon, Emily; Monaikul, Supida; Kostyniak, Paul J.; Chi, Lai Har; Schantz, Susan L.; Sable, Helen J. K.

    2013-01-01

    PCBs have long been known to affect dopamine (DA) function in the brain. The current study used an amphetamine behavioral sensitization paradigm in rats developmentally exposed to PCBs. Long-Evans rats were given perinatal exposure to 0, 3, or 6 mg/kg/day PCBs and behavioral sensitization to d-amphetamine (AMPH) was assessed in one adult male and female/litter. Non-exposed (control) males showed increasing locomotor activity to repeated injections of 0.5 mg/kg AMPH, typical of behavioral sensitization. PCB-exposed males showed greater activation to the initial acute AMPH injection, but sensitization occurred later and was blunted relative to controls. Sensitization in control females took longer to develop than in the males, but no exposure-related differences were observed. Analysis of whole brain and serum AMPH content following a final IP injection of 0.5 mg/kg revealed no differences among the exposure groups. Overall, these results indicated developmental PCB-exposure can alter the motor-stimulating effects of repeated AMPH injections. Males developmentally exposed to PCBs appeared to be pre-sensitized to AMPH, but quickly showed behavioral tolerance to the same drug dose. Results also revealed the behavioral effect was not due to exposure-induced alterations in AMPH metabolism following PCB exposure. PMID:23623962

  20. Role of copper accumulation in spontaneous renal carcinogenesis in Long-Evans Cinnamon rats.

    PubMed

    Kitaura, K; Chone, Y; Satake, N; Akagi, A; Ohnishi, T; Suzuki, Y; Izumi, K

    1999-04-01

    Spontaneous renal cell tumors in totals of 223 male and female Long-Evans Cinnamon (LEC) rats of 51-120 weeks old, 157 male F344 rats of 51-120 weeks old, and 14 male Long-Evans Agouti (LEA) rats of 51-70 weeks old were examined histologically. The incidences of renal cell tumors increased with age in male and female LEC rats, but no tumors developed in F344 or LEA rats. Dilated atypical tubules of the kidneys were observed at high incidence in aged LEC rats. Copper staining of LEC rat kidneys showed a positive reaction in proximal tubules of the cortex and the outer stripe of the medulla. The renal copper concentration of LEC rats reached a peak in the period of necrotizing hepatitis with renal tubular necrosis, and was higher than that in F344 rats for up to 106 weeks. In contrast, the renal iron concentration of LEC rats was lower than that in F344 rats except in the period of necrotizing hepatitis. Long-term treatment of LEC rats with D-penicillamine, a copper-chelating agent, inhibited accumulation of copper, but not iron, in the kidneys, and inhibited the development of karyomegaly of proximal tubules and dilated atypical tubules. These results suggest that persistent copper accumulation after toxic necrosis of tubules is the major cause of spontaneous renal carcinogenesis in LEC rats.

  1. THE EFFECT OF TARGETED KNOCKOUT MUTATION ON THE TRANSCRIPTIONAL PROFILE OF THE KIDNEY IN TSC2 MUTANT LONG-EVANS (EKER) RATS.

    EPA Science Inventory

    The effect of a targeted knockout mutation on the transcriptional profile of the kidney in
    Tsc2 mutant Long-Evans (Eker) rats.

    Renal cell carcinoma (RCC) is the most common tumor of the adult kidney, accounting
    for up to 80% of malignant renal neoplasms. Hereditary...

  2. Effects of prenatal exposure to a low dose atrazine metabolite mixture onpubertal timing and prostate development of male Long-Evans rats

    EPA Science Inventory

    Atrazine (ATR) is a chlorotriazine herbicide extensively used in the US and other countries. Studies examining the effects of adult or developmental ATR exposure on the mammary gland (MG) have used either the Sprague Dawley (SD) or Long-Evans (LE) rat, but no strain comparisons h...

  3. Lack of effect of nucleus accumbens dopamine D1 receptor blockade on consumption during the first two days of operant self-administration of sweetened ethanol in adult Long-Evans rats.

    PubMed

    Doherty, James M; Gonzales, Rueben A

    2015-09-01

    The mechanisms underlying ethanol self-administration are not fully understood; however, it is clear that ethanol self-administration stimulates nucleus accumbens dopamine release in well-trained animals. During operant sweetened ethanol self-administration behavior, an adaptation in the nucleus accumbens dopamine system occurs between the first and second exposure, paralleling a dramatic increase in sweetened ethanol intake, which suggests a single exposure to sweetened ethanol may be sufficient to learn the association between sweetened ethanol cues and its reinforcing properties. In the present experiment, we test the effects of blockade of nucleus accumbens dopamine D1 receptors on operant sweetened ethanol self-administration behavior during the first 2 days of exposure. Adult male Long-Evans rats were first trained to self-administer 10% sucrose (10S) across 6 days in an appetitive and consummatory operant model (appetitive interval: 10-min pre-drinking wait period and a lever response requirement of 4; consummatory interval: 20-min access to the drinking solution). After training on 10S, the drinking solution was switched to 10% sucrose plus 10% ethanol (10S10E); control rats continued drinking 10S throughout the experiment. Bilateral nucleus accumbens microinjections of the dopamine D1 antagonist, SCH-23390 (0, 1.0, or 3.0 μg/side), immediately preceded the first two sessions of drinking 10S10E. Results show that blocking nucleus accumbens dopamine D1 receptors has little or no influence on consumption during the first 2 days of exposure to the sweetened ethanol solution or maintenance of sucrose-only drinking. Furthermore, the high dose of SCH-23390, 3.0 μg/side, reduced open-field locomotor activity. In conclusion, we found no evidence to suggest that nucleus accumbens D1 receptor activation is involved in consumption of a sweetened ethanol solution during the first 2 days of exposure or maintenance of sucrose drinking, but rather D1 receptors seem

  4. Lack of effect of nucleus accumbens dopamine D1 receptor blockade on consumption during the first two days of operant self-administration of sweetened ethanol in adult Long-Evans rats

    PubMed Central

    Doherty, James M.; Gonzales, Rueben A.

    2014-01-01

    The mechanisms underlying ethanol self-administration are not fully understood; however, it is clear that ethanol self-administration stimulates nucleus accumbens dopamine release in well trained animals. During operant sweetened ethanol self-administration behavior, an adaptation in the nucleus accumbens dopamine system occurs between the first and second exposure paralleling a dramatic increase in sweetened ethanol intake, which suggests a single exposure to sweetened ethanol may be sufficient to learn the association between sweetened ethanol cues and its reinforcing properties. In the present experiment, we test the effects of blockade of nucleus accumbens dopamine D1 receptors on operant sweetened ethanol self-administration behavior during the first two days of exposure. Adult male Long-Evans rats were first trained to self-administer 10% sucrose (10S) across six days in an appetitive and consummatory operant model (appetitive interval: 10 min pre-drinking wait period and a lever response requirement of 4; consummatory interval: 20 min access to the drinking solution). After training on 10S, the drinking solution was switched to 10% sucrose plus 10% ethanol (10S10E); control rats remained drinking 10S throughout the experiment. Bilateral nucleus accumbens microinjections of the dopamine D1 antagonist, SCH-23390 (0, 1.0, or 3.0 μg/side), immediately preceded the first two sessions of drinking 10S10E. Results show that blocking nucleus accumbens dopamine D1 receptors has little or no influence on consumption during the first two days of exposure to the sweetened ethanol solution or maintenance of sucrose only drinking. Furthermore, the high dose of SCH-23390, 3.0 μg/side, reduced open field locomotor activity. In conclusion, we found no evidence to suggest that nucleus accumbens D1 receptor activation is involved in consumption of a sweetened ethanol solution during the first two days of exposure or maintenance of sucrose drinking, but rather D1 receptors

  5. Hepatocyte transplantation in the Long Evans Cinnamon rat model of Wilson's disease.

    PubMed

    Park, Seon Mee; Vo, Kim; Lallier, Michel; Cloutier, Alexis-Simon; Brochu, Pierre; Alvarez, Fernando; Martin, Steven R

    2006-01-01

    Wilson's disease (WD), caused by a mutation in the P-type copper transporting ATPase (Atp7b) gene, results in excessive accumulation of copper in the liver. Long Evans Cinnamon rats (LEC) bear a mutation in the atp7b gene and share clinical characteristics of human WD. To explore hepatocyte transplantation (HT) as therapy for metabolic liver diseases, 8-week-old LEC rats (n = 12) were transplanted by intrasplenic injection of hepatocytes from donor Long Evans (LE) rats. Immunosuppression was maintained with intraperitoneal tacrolimus. The success of HT was monitored at 24 weeks of life. Serum aminotransferases and bilirubin peaked at 14-21 weeks in both HT rats and nontransplanted controls, but at 24 weeks, survival was 97% in LEC-HT versus 63% in controls. All transplanted rats showed restored biliary copper excretion and reduced liver iron concentration associated with increased ceruloplasmin oxidase activity. Liver tissue expressed atp7b mRNA (11.9 +/- 13.6%) indicative of engraftment of normal cells in 7 of 12 HT rats, associated with a reduced liver copper concentration compared to untreated LEC rats. Periportal islets of normal appearing hepatocytes, recognized by atp7b antibody, were observed in transplanted livers while lobular host cells showed persistent pleomorphic changes and inflammatory infiltrates. In conclusion, transplantation of normal hepatocytes prevented fulminant hepatitis, reduces chronic inflammation, and improved 6-month survival in LEC rats. Engraftment of transplanted cells, which express atp7b mRNA, repopulated the recipient liver with normal functional capacity.

  6. Dietary copper triggers onset of fulminant hepatitis in the Long-Evans cinnamon rat model

    PubMed Central

    Siaj, Ramsi; Sauer, Vanessa; Stöppeler, Sandra; Spiegel, Hans-Ullrich; Köhler, Gabriele; Zibert, Andree; Schmidt, Hartmut HJ

    2012-01-01

    AIM: To investigate the impact of dietary copper given at different time points on the onset of fulminant hepatitis. METHODS: The Long-Evans cinnamon (LEC) rat model of Wilson’s disease (WD) was used to study the impact of high dietary copper (hCu) on the induction of fulminant hepatitis at early or late time points of life. High Cu diet was started in rat pups or in adults (month 5) for three months. Animals that received reduced dietary copper (rCu) throughout their lifetime served as a control. Hepatitis-associated serum markers (alanine aminotransferase, aspartate transaminase, bilirubin) were analyzed in animal groups receiving hCu or rCu. Liver copper content and liver histology were revealed at sacrifice. A set of 5 marker genes previously found to be affected in injured liver and which are related to angiogenesis (Vegfa), fat metabolism (Srebf1), extracellular matrix (Timp1), oxidative stress (Hmox1), and the cell cycle (Cdkn1a) were analyzed by real-time polymerase chain reaction. RESULTS: Regardless of the time point when hCu was started, LEC rats (35/36) developed fulminant hepatitis and died. Animals receiving rCu (36/36) remained healthy, did not develop hepatitis, and survived long term without symptoms of overt disease, although liver copper accumulated in adult animals (477 ± 75 μg/g). With regard to start of hCu, onset of fulminant hepatitis was significantly (P < 0.001) earlier in adults (35 ± 9 d) that showed pre-accumulation of liver copper as compared to the pup group (77 ± 15 d). Hepatitis-associated serum markers, liver copper and liver histology, as well as gene expression, were affected in LEC rats receiving hCu. However, except for early and rapid onset of hepatitis, biochemical and molecular markers were similar at the early and late time points of disease. CONCLUSION: Rapid onset of fulminant hepatitis in asymptomatic LEC rats with elevated liver copper suggests that there is a critical threshold of liver copper which is important

  7. Evolution of Exchangeable Copper and Relative Exchangeable Copper through the Course of Wilson's Disease in the Long Evans Cinnamon Rat

    PubMed Central

    Schmitt, Françoise; Podevin, Guillaume; Poupon, Joël; Roux, Jérôme; Legras, Pierre; Trocello, Jean-Marc; Woimant, France; Laprévote, Olivier; NGuyen, Tuan Huy; Balkhi, Souleiman El

    2013-01-01

    Background Wilson's disease (WD) is an inherited disorder of copper metabolism leading to liver failure and/or neurological impairment. Its diagnosis often remains difficult even with genetic testing. Relative exchangeable copper (REC) has recently been described as a reliable serum diagnostic marker for WD. Methodology/Principal Findings The aim of this study was to validate the use of REC in the Long Evans Cinnamon (LEC) rat, an animal model for WD, and to study its relevance under different conditions in comparison with conventional markers. Two groups of LEC rats and one group of Long-Evans (LE) rats were clinically and biologically monitored from 6 to 28 weeks of age. One group of LEC rats was given copper-free food. The other groups had normal food. Blood samples were collected each month and different serum markers for WD (namely ceruloplasmin oxidase activity, exchangeable copper (CuEXC), total serum copper and REC) and acute liver failure (serum transaminases and bilirubinemia) were tested. Every LEC rat under normal food developed acute liver failure (ALF), with 40% global mortality. Serum transaminases and bilirubinemia along with total serum copper and exchangeable copper levels increased with the onset of acute liver failure. A correlation was observed between CuEXC values and the severity of ALF. Cut-off values were different between young and adult rats and evolved because of age and/or liver failure. Only REC, with values >19%, was able to discriminate LEC groups from the LE control group at every time point in the study. REC sensitivity and specificity reached 100% in adults rats. Conclusions/Significance REC appears to be independent of demographic or clinical data in LEC rats. It is a very simple and reliable blood test for the diagnosis of copper toxicosis owing to a lack of ATP7B function. CuEXC can be used as an accurate biomarker of copper overload. PMID:24358170

  8. Pharmacokinetics of azidothymidine during late pregnancy in Long-Evans rats.

    PubMed

    Little, B B; Bawdon, R E; Christmas, J T; Sobhi, S; Gilstrap, L C

    1989-09-01

    Azidothymidine (Zidovudine) is used to treat symptomatic human immunodeficiency virus infection. It has the ability to reverse seropositivity as well as decrease serum viral titers, and perhaps decrease potential for transmission of the virus. An animal model (pregnant Long-Evans rats) was used to investigate the potential for placental transmission of azidothymidine. The drug crosses the placenta to reach concentrations in the placenta and fetus that are comparable to 75% and 58%, respectively, of those in the maternal serum by 2 hours after administration. By 4 to 6 hours after administration azidothymidine concentrations in the placenta and fetal liver significantly exceed maternal concentrations.

  9. Therapeutic effects of sericin on diabetic keratopathy in Otsuka Long-Evans Tokushima Fatty rats.

    PubMed

    Nagai, Noriaki; Ito, Yoshimasa

    2013-12-15

    An Otsuka Long-Evans Tokushima Fatty (OLETF) rat provides a useful model for studies to develop corneal wound healing drugs for use in diabetic keratopathy resulting from type 2 diabetes mellitus. We investigated the effects of sericin on corneal wound healing in OLETF rats. Corneal wounds were prepared by removal of the corneal epithelium and documented using a TRC-50X. Sericin was instilled into the eyes of rats five times a day following corneal abrasion. The plasma levels of glucose, triglycerides, cholesterol and insulin in 38 wk old OLETF rats were significantly higher than in normal control rats (LETO rats), and the rate of corneal wound healing in OLETF rats was slower than in normal rat, probably due to the suppression of cell migration and proliferation caused by high plasma glucose levels. The corneal wounds of OLETF rats instilled with saline showed almost complete healing 72 h after corneal epithelial abrasion. On the other hand, the instillation of sericin has a potent effect in promoting wound healing and wound size reduction in OLETF rats and the wounds showed almost complete healing at 48 h after abrasion. The sericin may be an effective and safe drug to promote corneal wound healing in diabetic keratopathy. PMID:24379918

  10. Tempol protects sleep-deprivation induced behavioral deficits in aggressive male Long-Evans rats.

    PubMed

    Solanki, Naimesh; Atrooz, Fatin; Asghar, Saman; Salim, Samina

    2016-01-26

    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 (24h) 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 (24h) 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. PMID:26724222

  11. Tempol protects sleep-deprivation induced behavioral deficits in aggressive male Long-Evans rats.

    PubMed

    Solanki, Naimesh; Atrooz, Fatin; Asghar, Saman; Salim, Samina

    2016-01-26

    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 (24h) 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 (24h) 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.

  12. Development of obesity in the Otsuka Long-Evans Tokushima Fatty rat

    PubMed Central

    Schroeder, Mariana; Zagoory-Sharon, Orna; Shbiro, Liat; Marco, Asaf; Hyun, Jayson; Moran, Timothy H.; Bi, Sheng

    2009-01-01

    Understanding the early factors affecting obesity development in males and females may help to prevent obesity and may lead to the discovery of more effective treatments for those already obese. The Otsuka Long-Evans Tokushima Fatty (OLETF) rat model of obesity is characterized by hyperphagia-induced obesity, due to a spontaneous lack of CCK1 receptors. In the present study, we focused on the behavioral and physiological aspects of obesity development from weaning to adulthood. We examined body weight, feeding efficiency, fat pad [brown, retroperitoneal, inguinal and epydidimal (in males)] weight, inguinal adipocyte size and number, leptin and oxytocin levels, body mass index, waist circumference, and females' estrous cycle structure. In the males, central hypothalamic gene expression was also examined. OLETF rats presented overall higher fat and leptin levels, larger adipocytes, and increased waist circumference and BMI from weaning until adulthood, compared with controls. Analysis of developmental patterns of gene expression for hypothalamic neuropeptides revealed peptide-specific patterns that may underlie or be a consequence of the obesity development. Analysis of the developmental trajectories toward obesity within the OLETF strain revealed that OLETF females developed obesity in a more gradual manner than the males, presenting delayed obesity-related “turning points,” with reduced adipocyte size but larger postweaning fat pads and increased adipocyte hyperplasia compared with the males. Intake decrease in estrus vs. proestrus was significantly less in OLETF vs. Long-Evans Tokushima Otsuka females. The findings highlight the importance of using different sex-appropriate approaches to increase the efficacy of therapeutic interventions in the treatment and prevention of chronic early-onset obesity. PMID:19793959

  13. Obesity in the Otsuka Long Evans Tokushima Fatty Rat: Mechanisms and Discoveries

    PubMed Central

    Bi, Sheng; Moran, Timothy H.

    2016-01-01

    Understanding the neural systems underlying the controls of energy balance has been greatly advanced by identifying the deficits and underlying mechanisms in rodent obesity models. The current review focuses on the Otsuka Long Evans Tokushima Fatty (OLETF) rat obesity model. Since its recognition in the 1990s, significant progress has been made in identifying the causes and consequences of obesity in this model. Fundamental is a deficit in the cholecystokinin (CCK)-1 receptor gene resulting in the absence of CCK-1 receptors in both the gastrointestinal track and the brain. OLETF rats have a deficit in their ability to limit the size of meals and in contrast to CCK-1 receptor knockout mice, do not compensate for this increase in the size of their spontaneous meals, resulting in hyperphagia. Prior to becoming obese and in response to pair feeding, OLETF rats have increased expression of neuropeptide Y (NPY) in the compact region of the dorsomedial hypothalamus (DMH), and this overexpression contributes to their overall hyperphagia. Study of the OLETF rats has revealed important differences in the organization of the DMH in rats and mice and elucidated previously unappreciated roles for DMH NPY in energy balance and glucose homeostasis. PMID:27512691

  14. A PHYSIOLOGICALLY-BASED PHARMACOKINETIC MODEL FOR TOLUENE IN THE LONG EVANS RAT: BODY COMPOSITION AND PHYSICAL ACTIVITY.

    EPA Science Inventory

    A physiologically-based pharmacokinetic (PBPK) model for inhaled toluene was developed for Long-Evans rats as a component of an exposure-dose-response (EDR) model for volatile organic compounds. The PBPK model was needed to link airborne toluene exposure to its concentration in b...

  15. EXPOSURE PARAMETERS FOR DELAYED PUBERTY AND MAMMARY GLAND DEVELOPMENT IN LONG-EVANS RATS EXPOSED IN UTERO TO ATRAZINE

    EPA Science Inventory

    Exposure Parameters For Delayed Puberty And Mammary Gland Development In Long-Evans Rats Exposed In Utero To Atrazine

    Jennifer L. Rayner1 and Suzanne E. Fenton2

    1 UNC-Chapel Hill, DESE, Chapel Hill, NC, and 2 RTD, USEPA, NHEERL/ORD, RTP,NC

    Prenatal exposure ...

  16. EFFECTS FROM GESTATIONAL EXPOSURE TO A MIXTURE OF ATRAZINE AND ITS BIOLOGICAL METABOLITES IN MALE LONG EVANS RATS

    EPA Science Inventory

    TITLE: EFFECTS FROM GESTATIONAL EXPOSURE TO A MIXTURE OF ATRAZINE AND ITS BIOLOGICAL METABOLITES IN MALE LONG EVANS RATS.
    Rolondo R. Enoch2, Sara N. Greiner 1, Geri L. Youngblood 1, Christine C. Davis 1, and Suzanne E. Fenton 1
    1 U.S. Environmental Protection Agency, ORD, ...

  17. EFFECTS FROM GESTATIONAL EXPOSURE TO A MIXTURE OF ATRAZINE AND IT'S BIOLOGICAL METABOLITES IN MALE LONG EVANS RATS

    EPA Science Inventory

    TITLE: EFFECTS FROM GESTATIONAL EXPOSURE TO A MIXTURE OF ATRAZINE AND ITS BIOLOGICAL METABOLITES IN MALE LONG EVANS RATS.
    Rolondo R. Enoch2, Sara N. Greiner 1, Geri L. Youngblood 1, Christine C. Davis 1, and Suzanne E. Fenton 1
    1 U.S. Environmental Protection Agency, ORD, ...

  18. EFFECTS FROM GESTATIONAL EXPOSURE TO A MIXTURE OF ATRAZINE AND ITS METABOLITES IN MALE LONG EVANS RATS

    EPA Science Inventory

    TITLE: EFFECTS FROM GESTATIONAL EXPOSURE TO A MIXTURE OF ATRAZINE AND IT'S BIOLOGICAL METABOLITES IN MALE LONG EVANS RATS. Suzanne E. Fenton 1, Sara N. Greiner 1, Geri L. Youngblood 1 and Christine C. Davis 1
    1 U.S. Environmental Protection Agency, Reproductive Toxicology Divi...

  19. EXPOSURE PARAMETERS NECESSARY FOR DELAYED PUBERTY AND MAMMARY GLAND DEVELOPMENT IN LONG-EVANS RATS EXPOSED IN UTERO TO ATRAZINE

    EPA Science Inventory

    Exposure Parameters Necessary For Delayed Puberty And Mammary Gland Development In Long-Evans Rats Exposed In Utero To Atrazine

    Jennifer L. Rayner1, 2, Carmen Wood2, and Suzanne E. Fenton2

    1 Department of Environmental Sciences and Engineering, School of Public Heal...

  20. Spontaneous hepatic copper accumulation in Long-Evans Cinnamon rats with hereditary hepatitis. A model of Wilson's disease.

    PubMed

    Li, Y; Togashi, Y; Sato, S; Emoto, T; Kang, J H; Takeichi, N; Kobayashi, H; Kojima, Y; Une, Y; Uchino, J

    1991-05-01

    Long-Evans Cinnamon (LEC) rats, an inbred strain of a mutant rat isolated from Long-Evans rats, develop hereditary hepatitis. To elucidate the role of copper metabolism in the development of the hepatitis in LEC rats, we examined the copper concentration in the tissues and serum levels of copper and ceruloplasmin. Copper concentration in the liver of LEC rats was over 40 times that of normal Long-Evans Agouti (LEA) rats, while the serum ceruloplasmin and copper concentrations in LEC rats decreased significantly. The hepatocytes of LEC rats show steatosis in cytoplasm and pleomorphism of mitochondria, resembling the histologic features of the liver in Wilson's disease. These findings suggest that the hereditary hepatitis in LEC rats is closely associated with copper toxicity, and may be dealing with a rat form of Wilson's disease. Thus the LEC rats will provide a unique and useful animal model for clarifying the mechanism and for developing treatment strategies for Wilson's disease and other abnormal copper metabolism in humans.

  1. Working-memory training: effects on delay discounting in male Long Evans rats.

    PubMed

    Renda, C Renee; Stein, Jeffrey S; Madden, Gregory J

    2015-01-01

    Delay discounting describes the devaluation of a reward as the delay to the receipt of the reward increases. Because steep delay discounting is robustly correlated with a number of behavioral problems (e.g., substance dependence, gambling) and some evidence suggests steep discounting precedes and predicts drug-taking in humans and rats, this study sought to experimentally reduce rats' delay discounting. Human stimulant-dependent participants given working-memory training reportedly decreased their rates of discounting relative to a sham-training group (Bickel, Yi, Landes, Hill, & Baxter, 2011). To evaluate the cross-species generality of this effect, 38 male Long-Evans rats, matched on pretraining delay-discounting rates, were randomly assigned to receive 140 sessions of working-memory training or sham training (which required no memory of the sample stimulus). Large between-group differences in working memory were observed after training; however, posttraining delay-discounting rates were undifferentiated across groups. Potential explanations for these findings are discussed.

  2. "Nice guys finish last": influence of mate choice on reproductive success in Long-Evans rats.

    PubMed

    Winland, C; Bolton, J L; Ford, B; Jampana, S; Tinker, J; Frohardt, R J; Guarraci, F A; Zewail-Foote, M

    2012-02-01

    The present study was designed to determine if male physiology and male reproductive behavior predict reproductive success in Long-Evans rats. Mating behavior was observed in sexually naïve, naturally cycling female rats during behavioral estrous that were given the opportunity to mate with two males simultaneously. DNA analysis of offspring born following these mating encounters was used to identify the paternity of each pup. In order to assess the effect of mate choice during these mating encounters on reproductive success, one male rat in each pair was categorized as the preferred mate if the female spent more time (>50%) with him during the mating test of the present study. Furthermore, each male in the pairs was categorized as "attractive" or "non-attractive" by computing the number of females that preferred each male across many mating tests. Similar to results reported in Lovell et al. (2007), during 76% of these mating tests the same male rat in each pair was preferred by different female rats. Overall attractiveness of individual male rats predicted reproductive success in the present study. Interestingly, "attractive" males sired significantly FEWER pups than "non-attractive" males. Neither behavioral (e.g., latency to first sexual stimulation, number of sexual stimulations) nor physiological measures (e.g., body weight, urinary testosterone levels) of male rats predicted their reproductive success. In conclusion, the present results indicate that certain features of some males are more attractive to females, but attractive males are at a reproductive disadvantage (as measured by the number of pups sired). Although basal urinary testosterone levels did not differ between males that sired the majority of pups in a litter and males that sired few or none of the pups in a litter, aggression and/or other physiological measures of fertility (e.g., penile reflexes) may differ between males that are attractive to females and those that have a reproductive

  3. "Nice guys finish last": influence of mate choice on reproductive success in Long-Evans rats.

    PubMed

    Winland, C; Bolton, J L; Ford, B; Jampana, S; Tinker, J; Frohardt, R J; Guarraci, F A; Zewail-Foote, M

    2012-02-01

    The present study was designed to determine if male physiology and male reproductive behavior predict reproductive success in Long-Evans rats. Mating behavior was observed in sexually naïve, naturally cycling female rats during behavioral estrous that were given the opportunity to mate with two males simultaneously. DNA analysis of offspring born following these mating encounters was used to identify the paternity of each pup. In order to assess the effect of mate choice during these mating encounters on reproductive success, one male rat in each pair was categorized as the preferred mate if the female spent more time (>50%) with him during the mating test of the present study. Furthermore, each male in the pairs was categorized as "attractive" or "non-attractive" by computing the number of females that preferred each male across many mating tests. Similar to results reported in Lovell et al. (2007), during 76% of these mating tests the same male rat in each pair was preferred by different female rats. Overall attractiveness of individual male rats predicted reproductive success in the present study. Interestingly, "attractive" males sired significantly FEWER pups than "non-attractive" males. Neither behavioral (e.g., latency to first sexual stimulation, number of sexual stimulations) nor physiological measures (e.g., body weight, urinary testosterone levels) of male rats predicted their reproductive success. In conclusion, the present results indicate that certain features of some males are more attractive to females, but attractive males are at a reproductive disadvantage (as measured by the number of pups sired). Although basal urinary testosterone levels did not differ between males that sired the majority of pups in a litter and males that sired few or none of the pups in a litter, aggression and/or other physiological measures of fertility (e.g., penile reflexes) may differ between males that are attractive to females and those that have a reproductive

  4. The effects of chronic photoperiod shifting on the physiology of female Long-Evans rats.

    PubMed

    Deibel, Scott H; Hong, Nancy S; Himmler, Stephanie M; McDonald, Robert J

    2014-04-01

    As the prevalence of shift work is increasing, it is important to elucidate the impact that shift work has on health. Because of the alternating work schedules present in rotating shift work and working at night, shift workers are in a chronic state of circadian disruption. Animal models of circadian disruption are useful because they offer more experimental control than the largely correlational human shift work studies. The effects of chronic circadian disruption on food preference, glucose tolerance, corticosterone secretion, and performance in a stress-inducing task were investigated in female Long-Evans rats. A 64-day photoperiod shifting paradigm was used to induce circadian disruption. Surprisingly, neither the photoperiod shifted animals, nor the control animals demonstrated a preference for either an unhealthy or healthy diet. Nor was there a difference between the groups in weight gained during photoperiod shifting. However, the photoperiod shifted rats gained significantly more weight than control animals, without eating more food during discriminative fear conditioning to context (DFCTC). Surprisingly, chronic photoperiod shifting appeared to facilitate retention in the DFCTC task. The photoperiod shifted animals also had increased serum glucose values during fasting and after a glucose challenge test. The photoperiod shifted animals only had elevated corticosterone during the final two phases of photoperiod shifting. This study demonstrates that chronic photoperiod shifting elicits weight gain when exposed to a stressful event and impairs glucose tolerance in the same individual. PMID:24631903

  5. The effects of chronic photoperiod shifting on the physiology of female Long-Evans rats.

    PubMed

    Deibel, Scott H; Hong, Nancy S; Himmler, Stephanie M; McDonald, Robert J

    2014-04-01

    As the prevalence of shift work is increasing, it is important to elucidate the impact that shift work has on health. Because of the alternating work schedules present in rotating shift work and working at night, shift workers are in a chronic state of circadian disruption. Animal models of circadian disruption are useful because they offer more experimental control than the largely correlational human shift work studies. The effects of chronic circadian disruption on food preference, glucose tolerance, corticosterone secretion, and performance in a stress-inducing task were investigated in female Long-Evans rats. A 64-day photoperiod shifting paradigm was used to induce circadian disruption. Surprisingly, neither the photoperiod shifted animals, nor the control animals demonstrated a preference for either an unhealthy or healthy diet. Nor was there a difference between the groups in weight gained during photoperiod shifting. However, the photoperiod shifted rats gained significantly more weight than control animals, without eating more food during discriminative fear conditioning to context (DFCTC). Surprisingly, chronic photoperiod shifting appeared to facilitate retention in the DFCTC task. The photoperiod shifted animals also had increased serum glucose values during fasting and after a glucose challenge test. The photoperiod shifted animals only had elevated corticosterone during the final two phases of photoperiod shifting. This study demonstrates that chronic photoperiod shifting elicits weight gain when exposed to a stressful event and impairs glucose tolerance in the same individual.

  6. Oxygen consumption and distribution in the Long-Evans rat retina

    PubMed Central

    Lau, Jennifer C.M.; Linsenmeier, Robert A.

    2012-01-01

    The purpose of this study was to investigate the oxygen distribution and consumption in the pigmented Long-Evans rat retina in vivo during dark and light adaptation, and to compare these results to previous work on cat and albino rat. Double-barreled microelectrodes recorded both intraretinal PO2 depth profiles and the electroretinogram (ERG), which was used to identify the boundaries of the retina. Light adaptation decreased photoreceptor oxygen consumption per unit volume (Qav) from 3.0±0.4 ml•100 g−1•min−1 (mean ± SEM) in darkness to 1.8±0.2 ml•100 g−1•min−1 and increased minimum outer retinal PO2 at the inner segments (Pmin) from 17.4±3.0 to 29.9±5.3 mmHg. The effects of light on outer retinal PO2 and Qav were similar to those previously observed in cat, monkey, and albino rats; however, dark-adapted Pmin was higher in rat than cat. The parameters derived from fitting the oxygen diffusion model to the rat data were compared to those from cat. Oxygen consumption of the inner segments (Q2) and choroidal PO2 (PC) in rat and cat were similar. Pmin was higher in rat than in cat for two reasons: first, rat photoreceptors have a shorter oxygen consuming region; and second, the retinal circulation supplied a greater fraction of consumed oxygen to rat photoreceptors. The average PO2 across the inner retina (PIR) was not different in dark adaptation (25.4±4.8 mm Hg) and light adaptation (28.8±5.4 mmHg) when measured from PO2 profiles. However, with the microelectrode stationary at 9–18% retinal depth, a small consistent decrease in PO2 occurred during illumination. Flickering light at 6 Hz decreased inner retinal PO2 significantly more than an equivalent steady illumination, suggesting that changes in blood flow did not completely compensate for increased metabolism. This study comprehensively characterized rat retinal oxygenation in both light and dark, and determined the similarities and differences between rat and cat retinas. PMID:22828049

  7. Mechanisms contributing to the regional haemodynamic effects of neurotensin in conscious, unrestrained Long Evans rats.

    PubMed Central

    Bachelard, H.; Gardiner, S. M.; Kemp, P. A.; Bennett, T.

    1992-01-01

    1. The regional haemodynamic effects of i.v. bolus doses of neurotensin (10-1000 ng) were assessed in conscious, unrestrained Long Evans rats chronically instrumented with miniaturized, pulsed Doppler probes. 2. Neurotensin caused increases in blood pressure, together with dose-related tachycardias and constrictions in the renal, superior mesenteric and hindquarters vascular beds. The tachycardia elicited by the 1000 ng dose of neurotensin was preceded by a transient bradycardia. 3. In the presence of phentolamine, the pressor effect of neurotensin (1000 ng) was converted into a hypotensive effect, accompanied by reduced tachycardic and constrictor responses in the renal, superior mesenteric and hindquarters vascular beds. The tachycardia was not preceded by a bradycardia. 4. In the presence of phentolamine and propranolol, the pressor and bradycardic responses to neurotensin were unaffected, whereas the tachycardia was abolished. The renal vasconstrictor effect was smaller, while the constrictions in the superior mesenteric and hindquarters vascular beds were not different from those in untreated rats. 5. In rats neonatally treated with capsaicin (50 mg kg-1, s.c.), the pressor effects elicited by neurotensin (300 and 1000 ng) were reduced as were the constrictor responses in the renal (at the dose of 300 ng), superior mesenteric (at the dose of 300 ng) and hindquarters (at both doses) vascular beds. The bradycardia elicited by neurotensin (1000 ng) was absent, whereas the tachycardia was potentiated. 6. The results indicate that in conscious, intact rats neurotensin appears to exert cardiovascular influences through activation of sympathoadrenal mechanisms and also through non-adrenergic effects on the heart, renal, superior mesenteric and hindquarters vascular beds. The latter effects appear to involve capsaicin-sensitive nerves. PMID:1596682

  8. Mechanisms contributing to the regional haemodynamic effects of neurotensin in conscious, unrestrained Long Evans rats.

    PubMed

    Bachelard, H; Gardiner, S M; Kemp, P A; Bennett, T

    1992-01-01

    1. The regional haemodynamic effects of i.v. bolus doses of neurotensin (10-1000 ng) were assessed in conscious, unrestrained Long Evans rats chronically instrumented with miniaturized, pulsed Doppler probes. 2. Neurotensin caused increases in blood pressure, together with dose-related tachycardias and constrictions in the renal, superior mesenteric and hindquarters vascular beds. The tachycardia elicited by the 1000 ng dose of neurotensin was preceded by a transient bradycardia. 3. In the presence of phentolamine, the pressor effect of neurotensin (1000 ng) was converted into a hypotensive effect, accompanied by reduced tachycardic and constrictor responses in the renal, superior mesenteric and hindquarters vascular beds. The tachycardia was not preceded by a bradycardia. 4. In the presence of phentolamine and propranolol, the pressor and bradycardic responses to neurotensin were unaffected, whereas the tachycardia was abolished. The renal vasconstrictor effect was smaller, while the constrictions in the superior mesenteric and hindquarters vascular beds were not different from those in untreated rats. 5. In rats neonatally treated with capsaicin (50 mg kg-1, s.c.), the pressor effects elicited by neurotensin (300 and 1000 ng) were reduced as were the constrictor responses in the renal (at the dose of 300 ng), superior mesenteric (at the dose of 300 ng) and hindquarters (at both doses) vascular beds. The bradycardia elicited by neurotensin (1000 ng) was absent, whereas the tachycardia was potentiated. 6. The results indicate that in conscious, intact rats neurotensin appears to exert cardiovascular influences through activation of sympathoadrenal mechanisms and also through non-adrenergic effects on the heart, renal, superior mesenteric and hindquarters vascular beds. The latter effects appear to involve capsaicin-sensitive nerves.

  9. Metallothionein and antioxidant enzymes in Long-Evans Cinnamon rats treated with zinc.

    PubMed

    Medici, Valentina; Santon, Alessandro; Sturniolo, Giacomo Carlo; D'Incà, Renata; Giannetto, Sabrina; Albergoni, Vincenzo; Irato, Paola

    2002-09-01

    The Long-Evans Cinnamon (LEC) rat is a mutant animal model for Wilson's disease. It is known that an abnormal accumulation of Cu and Fe in the liver and low concentrations of both ceruloplasmin and Cu in the serum occur in these rats. The accumulation of Cu is explained by the defective expression of the Cu-transporting P-type ATPase gene, homologous to the gene for Wilson's disease (ATP7B). The aim of this work was to clarify the action mechanism of Zn, and to verify the role that this metal plays in LEC rats in short-term treatment experiments (1 and 2 weeks) on concentrations of Cu, Zn, Fe, metallothionein (MT), 8-hydroxy-2'-deoxyguanosine (oh(8)dG) and on the activity of antioxidant enzymes. It is well known that Zn induces MT and has the ability to prevent redox-active metals, Cu and Fe, binding to and causing oxidative damage at active sites of Zn metalloenzymes and nonspecific binding sites on proteins. Zn administration reduces Cu and Fe transport from mucosal to serosal intestinal sides through competitive mechanisms. Our findings show that treatment with zinc acetate increases tissue Zn and MT contents and decreases Cu and Fe concentrations in the liver and kidneys, even if hepatic Zn and MT concentrations decrease with treatment period. Induction of MT synthesis by Zn contributes to the reduction in free radicals produced by Cu and Fe. We also observed that the superoxide dismutase (SOD)activity in liver decreases with treatment duration in association with the Cu and Fe liver decrease. However, the SOD activity in kidney increases in untreated rats at 2 weeks relative to those untreated for 1 week.

  10. Behavioral Phenotyping of Juvenile Long-Evans and Sprague-Dawley Rats: Implications for Preclinical Models of Autism Spectrum Disorders

    PubMed Central

    Ku, Katherine M.; Weir, Ruth K.; Silverman, Jill L.; Berman, Robert F.; Bauman, Melissa D.

    2016-01-01

    The laboratory rat is emerging as an attractive preclinical animal model of autism spectrum disorder (ASD), allowing investigators to explore genetic, environmental and pharmacological manipulations in a species exhibiting complex, reciprocal social behavior. The present study was carried out to compare two commonly used strains of laboratory rats, Sprague-Dawley (SD) and Long-Evans (LE), between the ages of postnatal day (PND) 26–56 using high-throughput behavioral phenotyping tools commonly used in mouse models of ASD that we have adapted for use in rats. We detected few differences between young SD and LE strains on standard assays of exploration, sensorimotor gating, anxiety, repetitive behaviors, and learning. Both SD and LE strains also demonstrated sociability in the 3-chamber social approach test as indexed by spending more time in the social chamber with a constrained age/strain/sex matched novel partner than in an identical chamber without a partner. Pronounced differences between the two strains were, however, detected when the rats were allowed to freely interact with a novel partner in the social dyad paradigm. The SD rats in this particular testing paradigm engaged in play more frequently and for longer durations than the LE rats at both juvenile and young adult developmental time points. Results from this study that are particularly relevant for developing preclinical ASD models in rats are threefold: (i) commonly utilized strains exhibit unique patterns of social interactions, including strain-specific play behaviors, (ii) the testing environment may profoundly influence the expression of strain-specific social behavior and (iii) simple, automated measures of sociability may not capture the complexities of rat social interactions. PMID:27351457

  11. Behavioral Phenotyping of Juvenile Long-Evans and Sprague-Dawley Rats: Implications for Preclinical Models of Autism Spectrum Disorders.

    PubMed

    Ku, Katherine M; Weir, Ruth K; Silverman, Jill L; Berman, Robert F; Bauman, Melissa D

    2016-01-01

    The laboratory rat is emerging as an attractive preclinical animal model of autism spectrum disorder (ASD), allowing investigators to explore genetic, environmental and pharmacological manipulations in a species exhibiting complex, reciprocal social behavior. The present study was carried out to compare two commonly used strains of laboratory rats, Sprague-Dawley (SD) and Long-Evans (LE), between the ages of postnatal day (PND) 26-56 using high-throughput behavioral phenotyping tools commonly used in mouse models of ASD that we have adapted for use in rats. We detected few differences between young SD and LE strains on standard assays of exploration, sensorimotor gating, anxiety, repetitive behaviors, and learning. Both SD and LE strains also demonstrated sociability in the 3-chamber social approach test as indexed by spending more time in the social chamber with a constrained age/strain/sex matched novel partner than in an identical chamber without a partner. Pronounced differences between the two strains were, however, detected when the rats were allowed to freely interact with a novel partner in the social dyad paradigm. The SD rats in this particular testing paradigm engaged in play more frequently and for longer durations than the LE rats at both juvenile and young adult developmental time points. Results from this study that are particularly relevant for developing preclinical ASD models in rats are threefold: (i) commonly utilized strains exhibit unique patterns of social interactions, including strain-specific play behaviors, (ii) the testing environment may profoundly influence the expression of strain-specific social behavior and (iii) simple, automated measures of sociability may not capture the complexities of rat social interactions. PMID:27351457

  12. Behavioral Phenotyping of Juvenile Long-Evans and Sprague-Dawley Rats: Implications for Preclinical Models of Autism Spectrum Disorders.

    PubMed

    Ku, Katherine M; Weir, Ruth K; Silverman, Jill L; Berman, Robert F; Bauman, Melissa D

    2016-01-01

    The laboratory rat is emerging as an attractive preclinical animal model of autism spectrum disorder (ASD), allowing investigators to explore genetic, environmental and pharmacological manipulations in a species exhibiting complex, reciprocal social behavior. The present study was carried out to compare two commonly used strains of laboratory rats, Sprague-Dawley (SD) and Long-Evans (LE), between the ages of postnatal day (PND) 26-56 using high-throughput behavioral phenotyping tools commonly used in mouse models of ASD that we have adapted for use in rats. We detected few differences between young SD and LE strains on standard assays of exploration, sensorimotor gating, anxiety, repetitive behaviors, and learning. Both SD and LE strains also demonstrated sociability in the 3-chamber social approach test as indexed by spending more time in the social chamber with a constrained age/strain/sex matched novel partner than in an identical chamber without a partner. Pronounced differences between the two strains were, however, detected when the rats were allowed to freely interact with a novel partner in the social dyad paradigm. The SD rats in this particular testing paradigm engaged in play more frequently and for longer durations than the LE rats at both juvenile and young adult developmental time points. Results from this study that are particularly relevant for developing preclinical ASD models in rats are threefold: (i) commonly utilized strains exhibit unique patterns of social interactions, including strain-specific play behaviors, (ii) the testing environment may profoundly influence the expression of strain-specific social behavior and (iii) simple, automated measures of sociability may not capture the complexities of rat social interactions.

  13. [Overgrowth and DNA synthesis of neuroepithelium in embryonic stages of induced Long-Evans rat myeloschisis].

    PubMed

    Chono, Y

    1993-01-01

    Overgrowth of the myeloschisis, namely the excessive amount of the neural plate tissue, has been reported in the human myeloschisis. However, it is still debatable how the overgrowth develops and whether the overgrowth is the cause, or the secondary effect of spinal dysraphism. The author induced myeloschisis in the fetuses of Long-Evans rats by the administration of ethylenethiourea (ETU) to pregnant rats on day 10 of gestation. The fetuses were removed 1 hour after the treatment with bromodeoxyuridine (BrdU) to the dams on day 14 and 21. The fetuses were fixed in alcohol and embedded in paraffin. H-E staining and the immunohistologic examination were performed on the staining patterns to anti-neurofilament (NFP), anti-glial fibrillary acidic protein (GFAP) and anti-BrdU antibody by ABC method. On day 14, the lateral portion of everted neural plate showed a loose arrangement of cells and there was rosette formation in the mesoderm. On day 21, cell necrosis was observed at the dorsolateral portion of myeloschisis, although the ventral portion showed almost normal cytoarchitecture and was positive to NFP and GFAP. The cause of myeloschisis in this model is supposed to be the local and direct cytotoxic effect of ETU to neuro-ectodermal junction. On day 14, control animals contained few BrdU-incorporated cells at the basal plate of neural tube. In contrast, everted neural plate showed an active uptake of BrdU diffusely in the subependymal matrix layer cells. Overgrowth was not yet identified. On day 21, overgrowth of myeloschisis was found in spite of a few positive cells to BrdU which was identical to the control animals. These findings seem to suggest that cells in the myeloschisis retain their ability of DNA synthesis for longer periods of development and overgrowth found on day 21 is possibly a secondary effect of spinal dysraphism in this model.

  14. Mechanism of enhanced lipid peroxidation in the liver of Long-Evans cinnamon (LEC) rats.

    PubMed

    Yamamoto, H; Hirose, K; Hayasaki, Y; Masuda, M; Kazusaka, A; Fujita, S

    1999-11-01

    The Long-Evans Cinnamon (LEC) rat is a mutant strain of rats that accumulate copper (Cu) in the liver in much the same way as individuals who suffer from Wilson's disease (WD) and has been suggested as a model for this disease. Lipid peroxidation (LPO) is considered to be involved in the toxic action of Cu in the livers of LEC rats. We investigated the mechanism of LPO in the livers of LEC rats showing apparent signs of hepatitis. Several-fold higher LPO levels were observed in post-mitochondrial supernatant (S-9) fraction of livers from hepatitic LEC rats than in those from Wistar rats. To mimic living cells, we introduced NADPH-generating system (NADPH-gs) into the S-9 incubation system. Thus was ensured a constant supply of NADPH to vital enzymes that may be directly or indirectly involved in the generation and/or elimination of reactive oxygen species (ROSs), such as glutathione reductase (GSSG-R), which require NADPH for their reactions. The levels of LPO in liver S-9 from hepatitic LEC rats were further increased by incubating liver S-9 at 37 degrees C in the presence of NADPH-gs. This increase was inhibited by EDTA, butylated hydroxytoluene (BHT), and catalase (CAT), suggesting that some metal, most likely the accumulated Cu, and ROSs derived from hydrogen peroxide (H2O2) are involved in the increased levels of LPO in the livers of hepatitic LEC rats. The requirement of NADPH-gs for enhanced LPO in the livers of hepatitic LEC rats indicates the consumption of NADPH during reactions leading to LPO. It is known that H2O2, and consequently hydroxyl radical are generated during Cu-catalyzed glutathione (GSH) oxidation. The cyclic regeneration of GSH from GSSG by NADPH-dependent GSSG-R in the presence of NADPH-gs may cause sustained generation of hydroxyl radical in the presence of excess free Cu. The generation of H2O2 in S-9 fraction of livers from hepatitic LEC rats was observed to be significantly higher than that in S-9 fraction of livers from non

  15. Methylphenidate alters flash-evoked potentials, body temperature, and behavior in Long-Evans rats.

    PubMed

    Hetzler, Bruce E; Meckel, Katherine R; Stickle, Bruce A

    2014-01-01

    This experiment examined the effects of methylphenidate hydrochloride on flash-evoked potentials (FEPs) recorded from the visual cortex (VC) and superior colliculus (SC) of chronically implanted male Long-Evans rats, as well as on body temperature and open field behavior. FEPs were recorded at 10, 20 and 40 min following intraperitoneal injections of saline, and of doses of 0.7, 2.9, and 11.6 mg/kg methylphenidate on separate days. The 0.7 mg/kg dose did not produce significant effects. In the VC, following administration of the 11.6 mg/kg dose of methylphenidate the amplitude of components P83, N146, and P232 decreased, the amplitude of component N64 briefly increased and components P23, N30, N40, and P48 were unchanged in amplitude. In the SC, component P29 was unaffected, while components P38 and N51 were reduced in amplitude by the 11.6 mg/kg dose of methylphenidate. Peak latencies of components N40, P48, P83, and N146 in the VC and component P38 in the SC were increased by the 11.6 mg/kg dose of methylphenidate. When body temperature was recorded 45 min after drug administration, a mild dose-dependent hypothermia was found with the 2.9 and 11.6 mg/kg methylphenidate doses, suggesting that this may have contributed to the increased latencies. In subsequent open field observations, both line crossings and rearings were significantly increased by the 11.6 mg/kg dose. Increased movement into the center of the testing area was also observed, which could be a sign of increased exploration and reduced anxiety following methylphenidate.

  16. Atrazine-induced reproductive tract alterations after transplacental and/or lactational exposure in male Long-Evans rats

    SciTech Connect

    Rayner, Jennifer L.; Enoch, Rolondo R.; Wolf, Douglas C.; Fenton, Suzanne E. . E-mail: fenton.suzanne@epa.gov

    2007-02-01

    Studies showed that early postnatal exposure to the herbicide atrazine (ATR) delayed preputial separation (PPS) and increased incidence of prostate inflammation in adult Wistar rats. A cross-fostering paradigm was used in this study to determine if gestational exposure to ATR would also result in altered puberty and reproductive tissue effects in the male rat. Timed-pregnant Long-Evans (LE) rats were dosed by gavage on gestational days (GD) 15-19 with 100 mg ATR/kg body weight (BW) or 1% methylcellulose (controls, C). On postnatal day (PND)1, half litters were cross-fostered, creating 4 treatment groups; C-C, ATR-C, C-ATR, and ATR-ATR (transplacental-milk as source, respectively). On PND4, male offspring in the ATR-ATR group weighed significantly less than the C-C males. ATR-ATR male pups had significantly delayed preputial separation (PPS). BWs at PPS for C-ATR and ATR-ATR males were reduced by 6% and 9%, respectively, from that of C-C. On PND120, lateral prostate weights of males in the ATR-ATR group were significantly increased over C-C. Histological examination of lateral and ventral prostates identified an increased distribution of inflammation in the lateral prostates of C-ATR males. By PND220, lateral prostate weights were significantly increased for ATR-C and ATR-ATR, but there were no significant changes in inflammation in either the lateral or ventral prostate. These results suggest that in LE rats, gestational ATR exposure delays PPS when male offspring suckle an ATR dam, but leads to increased lateral prostate weight via transplacental exposure alone. Inflammation present at PND120 does not increase in severity with time.

  17. Changes in plasma glucose in Otsuka Long-Evans Tokushima Fatty rats after oral administration of maple syrup.

    PubMed

    Nagai, Noriaki; Yamamoto, Tetsushi; Tanabe, Wataru; Ito, Yoshimasa; Kurabuchi, Satoshi; Mitamura, Kuniko; Taga, Atsushi

    2015-01-01

    We investigate whether maple syrup is a suitable sweetener in the management of type 2 diabetes using the Otsuka Long-Evans Tokushima Fatty (OLETF) rat. The enhancement in plasma glucose (PG) and glucose absorption in the small intestine were lower after the oral administration of maple syrup than after sucrose administration in OLETF rats, and no significant differences were observed in insulin levels. These data suggested that maple syrup might inhibit the absorption of glucose from the small intestine and preventing the enhancement of PG in OLETF rats. Therefore, maple syrup might help in the prevention of type 2 diabetes.

  18. Effects of Moderate Alcohol Intake in the Bladder of the Otsuka Long Evans Tokushima Fatty Diabetic Rats

    PubMed Central

    Bae, Woong Jin; Choi, Yong Sun; Kim, Su Jin; Cho, Hyuk Jin; Hong, Sung Hoo; Kim, Sae Woong; Hwang, Tae-Kon; Kim, Dai Jin

    2015-01-01

    Diabetes is related with a number of cystopathic complications. However, there have been no studies about the influence of alcohol consumption in the bladder of type 2 diabetes. Thus, we investigated the effect of moderate alcohol intake in the bladder of the Otsuka Long Evans Tokushima Fatty (OLETF) diabetic rat. The non-diabetic Long-Evans Tokushima Otsuka (LETO, n=14) and the OLETF control group (n=14) were fed an isocaloric diet; the LETO (n=14) and the OLETF ethanol group (n=14) were fed 36% ethanol 7 g/kg/day. After ten weeks, muscarinic receptors, RhoGEFs, myogenic change, and the level of oxidative stress were evaluated. Moderate alcohol intake significantly decreased excessive muscarinic receptor and Rho kinase expressions in the OLETF rats compared with the LETO rats. In addition, iNOS and collagen expression were not changed in the OLETF rats in spite of alcohol consumption. Superoxide dismutase levels, which is involved in antioxidant defense, in the LETO rats were significantly decreased after alcohol consumption, however those in the OLETF rats were similar. Moderate alcohol consumption reduces the oxidative stress, and may prevent molecular and pathologic changes of the bladder of rats with type 2 diabetes. PMID:26339173

  19. Effects of Moderate Alcohol Intake in the Bladder of the Otsuka Long Evans Tokushima Fatty Diabetic Rats.

    PubMed

    Bae, Woong Jin; Choi, Yong Sun; Kim, Su Jin; Cho, Hyuk Jin; Hong, Sung Hoo; Kim, Sae Woong; Hwang, Tae-Kon; Kim, Dai Jin; Lee, Ji Youl

    2015-09-01

    Diabetes is related with a number of cystopathic complications. However, there have been no studies about the influence of alcohol consumption in the bladder of type 2 diabetes. Thus, we investigated the effect of moderate alcohol intake in the bladder of the Otsuka Long Evans Tokushima Fatty (OLETF) diabetic rat. The non-diabetic Long-Evans Tokushima Otsuka (LETO, n=14) and the OLETF control group (n=14) were fed an isocaloric diet; the LETO (n=14) and the OLETF ethanol group (n=14) were fed 36% ethanol 7 g/kg/day. After ten weeks, muscarinic receptors, RhoGEFs, myogenic change, and the level of oxidative stress were evaluated. Moderate alcohol intake significantly decreased excessive muscarinic receptor and Rho kinase expressions in the OLETF rats compared with the LETO rats. In addition, iNOS and collagen expression were not changed in the OLETF rats in spite of alcohol consumption. Superoxide dismutase levels, which is involved in antioxidant defense, in the LETO rats were significantly decreased after alcohol consumption, however those in the OLETF rats were similar. Moderate alcohol consumption reduces the oxidative stress, and may prevent molecular and pathologic changes of the bladder of rats with type 2 diabetes.

  20. S-Allyl cysteine improves nonalcoholic fatty liver disease in type 2 diabetes Otsuka Long-Evans Tokushima Fatty rats via regulation of hepatic lipogenesis and glucose metabolism.

    PubMed

    Takemura, Shigekazu; Minamiyama, Yukiko; Kodai, Shintaro; Shinkawa, Hiroji; Tsukioka, Takuma; Okada, Shigeru; Azuma, Hideki; Kubo, Shoji

    2013-09-01

    It is important to prevent and improve diabetes mellitus and its complications in a safe and low-cost manner. S-Allyl cysteine, an aged garlic extract with antioxidant activity, was investigated to determine whether S-allyl cysteine can improve type 2 diabetes in Otsuka Long-Evans Tokushima Fatty rats with nonalcoholic fatty liver disease. Male Otsuka Long-Evans Tokushima Fatty rats and age-matched Long-Evans Tokushima Otsuka rats were used and were divided into two groups at 29 weeks of age. S-Allyl cysteine (0.45% diet) was administered to rats for 13 weeks. Rats were killed at 43 weeks of age, and detailed analyses were performed. S-Allyl cysteine improved hemoglobinA1c, blood glucose, triglyceride, and low-density lipoprotein cholesterol levels. Furthermore, S-allyl cysteine normalized plasma insulin levels. S-Allyl cysteine activated the mRNA and protein expression of both peroxisome proliferator-activated receptor α and γ, as well as inhibiting pyruvate dehydrogenase kinase 4 in Otsuka Long-Evans Tokushima Fatty rat liver. Sterol regulatory element-binding protein 1c and forkhead box O1 proteins were normalized by S-allyl cysteine in Otsuka Long-Evans Tokushima Fatty rat liver. In conclusions, these findings support the hypothesis that S-allyl cysteine has diabetic and nonalcoholic fatty liver disease therapeutic potential as a potent regulating agent against lipogenesis and glucose metabolism. PMID:24062606

  1. Electrocardiogram and cardiac function in a longitudinal study of copper deficiency in the Long-Evans rat

    SciTech Connect

    Zhiming Liao, Hamlin, R.; Medeiros, D.M. )

    1991-03-11

    Weanling Long-Evans rats were fed either copper-adequate or -restricted diets for varying periods of time up to 6 wk. Beginning at 2 wk after weaning, and weekly thereafter, 5 rats from each diet were evaluated for cardiac function and ECG activity and sacrificed. ECG traces revealed indications of cardiac failure at week 3 in rats fed the copper-restricted diet at which time concentric cardiac hypertrophy was evident. Prolonged P-R and Q-T intervals and greater QRS height and higher voltages were observed in copper-restricted rats. However, + and {minus} dP/dt max did not differ by diet copper treatment for any of the time intervals studied, nor was any notable difference in total left developed ventricular pressure apparent. These results suggest that the onset of cardiac dysfunction in copper deficiency is rapid, with both dysfunction and hypertrophy apparent within 3 weeks after copper restriction.

  2. Redox regulation of apurinic/apyrimidinic endonuclease 1 activity in Long-Evans Cinnamon rats during spontaneous hepatitis.

    PubMed

    Karmahapatra, Soumendra Krishna; Saha, Tapas; Adhikari, Sanjay; Woodrick, Jordan; Roy, Rabindra

    2014-03-01

    The Long-Evans Cinnamon (LEC) rat is an animal model for Wilson's disease. This animal is genetically predisposed to copper accumulation in the liver, increased oxidative stress, accumulation of DNA damage, and the spontaneous development of hepatocellular carcinoma. Thus, this animal model is useful for studying the relationship of endogenous DNA damage to spontaneous carcinogenesis. In this study, we have investigated the apurinic/apyrimidinic endonuclease 1 (APE1)-mediated excision repair of endogenous DNA damage, apurinic/apyrimidinic (AP)-sites, which is highly mutagenic and implicated in human cancer. We found that the activity was reduced in the liver extracts from the acute hepatitis period of LEC rats as compared with extracts from the age-matched Long-Evans Agouti rats. The acute hepatitis period had also a heightened oxidative stress condition as assessed by an increase in oxidized glutathione level and loss of enzyme activity of glyceraldehyde 3-phosphate dehydrogenase, a key redox-sensitive protein in cells. Interestingly, the activity reduction was not due to changes in protein expression but apparently by reversible protein oxidation as the addition of reducing agents to extracts of the liver from acute hepatitis period reactivated APE1 activity and thus, confirmed the oxidation-mediated loss of APE1 activity under increased oxidative stress. These findings show for the first time in an animal model that the repair mechanism of AP-sites is impaired by increased oxidative stress in acute hepatitis via redox regulation which contributed to the increased accumulation of mutagenic AP-sites in liver DNA.

  3. Age-related dose response of selected reproductive parameters to acute cadmium chloride exposure in the male Long-Evans rat

    EPA Science Inventory

    Groups of Long Evans rats 30, 50, or 70 days old were injected subcutaneously (s.c.) with a single dose of between 0 and 52 micromoles Cd/Kg as cadmium (CD) chloride. Sixty days post dosing and two hours prior to sacrifice the rats were injected s.c. with 100 IU of hCG to stimula...

  4. Hepatic iron deprivation prevents spontaneous development of fulminant hepatitis and liver cancer in Long-Evans Cinnamon rats.

    PubMed

    Kato, J; Kobune, M; Kohgo, Y; Sugawara, N; Hisai, H; Nakamura, T; Sakamaki, S; Sawada, N; Niitsu, Y

    1996-08-15

    Several clinical studies have suggested that excess hepatic iron accumulation is a progressive factor in some liver diseases including chronic viral hepatitis and hemochromatosis. However, it is not known whether iron-induced hepatotoxicity may be directly involved in hepatitis, cirrhosis, and liver cancer. The Long-Evans Cinnamon (LEC) rat, which accumulates excess copper in the liver as in patients with Wilson's disease, is of a mutant strain displaying spontaneous hemolysis, hepatitis, and liver cancer. We found previously that LEC rats harbored an additional abnormality: accumulation of as much iron as copper in the liver. In the present study, we compared the occurrence of hepatitis and liver cancer in LEC rats fed an iron-deficient diet (ID) with those in rats fed a regular diet (RD). The RD group showed rapid increments of hepatic iron concentrations as the result of hemolysis, characteristics of fulminant hepatitis showing apoptosis, and a 53% mortality rate. However, no rats in the ID group died of fulminant hepatitis. Hepatic iron, especially "free" iron concentration and the extent of hepatic fibrosis in the ID group were far less than those of the RD group. At week 65, all rats in the RD group developed liver cancer, whereas none did in the ID group. These results suggest that the accumulation of iron, possibly by virtue of synergistic radical formation with copper, plays an essential role in the development of fulminant hepatitis, hepatic fibrosis, and subsequent hepatocarcinogenesis in LEC rats.

  5. Strain Differences in Dimethylbenz[a]anthracene-Induced Mammary Tumor Incidence in Long Evans and Sprague Dawley Rat Offspring Following Prenatal Atrazine Exposure

    EPA Science Inventory

    It has been shown that prenatal exposure to the chlorotriazine herbicide atrazine (ATR) during mammary bud outgrowth (late gestation) delays postnatal mammary epithelial progression in Long Evans (LE) rats. Our laboratory has recently found that prenatal exposure to ATR also effe...

  6. Mechanism of hepatorenal syndrome in rats of Long-Evans Cinnamon strain, an animal model of fulminant Wilson's disease.

    PubMed

    Nomiyama, K; Nomiyama, H; Kameda, N; Tsuji, A; Sakurai, H

    1999-02-15

    Rats of Long-Evans Cinnamon (LEC) strain were used as a hepatorenal syndrome model of fulminant Wilson's disease. Copper levels in the kidneys increased markedly from 16 to 126 microg Cu/g from 12 to 16 weeks, and remained at the same level at 16 and 19 weeks when the rats suffered from severe renal dysfunction and also at 20 weeks in some other normal rats. The above findings imply that the renal dysfunction may have been induced independently of the copper level in the kidneys. The present study suggested the following mechanism: immediately after copper-induced hepatic dysfunction, plasma copper-metallothionein (CuMT), which was released from the liver, became elevated. The elevation was closely related to the increases in alkaline phosphatase, glucose and amino acids, all in the urine. The above findings suggest that plasma CuMT, which was released from the liver into the blood upon copper-induced hepatic dysfunction, was subsequently filtered at the glomeruli due to its smaller molecular weight, and then caused dysfunction of the brush border membrane of the renal proximal tubules probably after splitting into radical copper and amino acids in acidic vesicles close to the membrane. The critical concentration of plasma CuMT required to induce renal dysfunction was estimated as 1 microg Cu/l.

  7. METABOLIC RATE AS A FUNCTION OF AGE IN BROWN NORWAY AND LONG-EVANS RATS.

    EPA Science Inventory

    Brown Norway (BN) rats are commonly used in aging studies but relatively little is known on their metabolism as it varies with age. In fact, there is considerable disagreement on the wholebody metabolism of aging rats with some studies indicating a decrease and others showing an...

  8. Stress facilitates late reversal learning using a touchscreen-based visual discrimination procedure in male Long Evans rats.

    PubMed

    Bryce, Courtney A; Howland, John G

    2015-02-01

    The stress response is essential to the survival of all species as it maintains internal equilibrium and allows organisms to respond to threats in the environment. Most stress research has focused on the detrimental impacts of stress on cognition and behavior. Reversal learning, which requires a change in response strategy based on one dimension of the stimuli, is one type of behavioral flexibility that is facilitated following some brief stress procedures. The current study investigated a potential mechanism underlying this facilitation by blocking glucocorticoid receptors (GRs) during stress. Thirty-seven male Long Evans rats learned to discriminate between two images on a touchscreen, one of which was rewarded. Once a criterion was reached, rats received stress (30 min of restraint stress or no stress) and drug (GR antagonist RU38486 or vehicle) administration prior to each of the first 3 days of reversal learning. We expected that stress would facilitate reversal learning and RU38486 (10 mg/kg) would prevent this facilitation in both early (<50% correct in one session) and late (>50% correct in one session) stages of reversal learning. Results showed that stressed rats performed better than unstressed rats (fewer days for late reversal, fewer correction trials, and fewer errors) in the late but not early stage of reversal learning. RU38486 did not block the facilitation of RL by stress, although it dramatically increased response, but not reward, latencies. These results confirm the facilitation of late reversal by stress in a touchscreen-based operant task in rats and further our understanding of how stress affects higher level cognitive functioning and behavior. PMID:25251839

  9. Stress facilitates late reversal learning using a touchscreen-based visual discrimination procedure in male Long Evans rats.

    PubMed

    Bryce, Courtney A; Howland, John G

    2015-02-01

    The stress response is essential to the survival of all species as it maintains internal equilibrium and allows organisms to respond to threats in the environment. Most stress research has focused on the detrimental impacts of stress on cognition and behavior. Reversal learning, which requires a change in response strategy based on one dimension of the stimuli, is one type of behavioral flexibility that is facilitated following some brief stress procedures. The current study investigated a potential mechanism underlying this facilitation by blocking glucocorticoid receptors (GRs) during stress. Thirty-seven male Long Evans rats learned to discriminate between two images on a touchscreen, one of which was rewarded. Once a criterion was reached, rats received stress (30 min of restraint stress or no stress) and drug (GR antagonist RU38486 or vehicle) administration prior to each of the first 3 days of reversal learning. We expected that stress would facilitate reversal learning and RU38486 (10 mg/kg) would prevent this facilitation in both early (<50% correct in one session) and late (>50% correct in one session) stages of reversal learning. Results showed that stressed rats performed better than unstressed rats (fewer days for late reversal, fewer correction trials, and fewer errors) in the late but not early stage of reversal learning. RU38486 did not block the facilitation of RL by stress, although it dramatically increased response, but not reward, latencies. These results confirm the facilitation of late reversal by stress in a touchscreen-based operant task in rats and further our understanding of how stress affects higher level cognitive functioning and behavior.

  10. Brain energy consumption in ethanol-treated, Long-Evans rats.

    PubMed

    Viña, J R; Salus, J E; DeJoseph, M R; Pallardo, F; Towfighi, J; Hawkins, R A

    1991-06-01

    The cerebral metabolic rate of glucose utilization (CMRGlc) was measured in rats fed liquid diets containing ethanol for 8 wk, after removal of ethanol from the diet and after acute ethanol intoxication. Control rats were pair fed the liquid diets containing isoenergetic amounts of dextrin-maltose. Quantitative autogradiography using [6-14C]glucose measured CMRGlc at the level of individual structures. Digital image techniques created stereograms of brain energy consumption from the autoradiographs. These techniques provided information about CMRGlc throughout the brain. Rats given the ethanol liquid diet drank constantly throughout the day and night. Neuropathological examination of brain revealed no abnormalities from ethanol consumption. Acute ethanol administration to control rats produced a decrease in CMRGlc throughout the brain that was most prominent in structures concerning auditory, visual, memory and motor functions. Chronic ethanol consumption did not reduce CMRGlc to the same degree as acute ethanol intoxication; in fact, it affected only a few structures. The removal of ethanol from chronic ethanol-treated rats for a period of 18 h caused CMRGlc to rise above control values throughout the brain. However, there were no seizures or other evidence of brain dysfunction.

  11. A PHYSIOLOGICALLY-BASED PHARMACOKINETIC MODEL FOR TRICHLOROETHYLENE WITH SPECIFICITY FOR THE LONG EVANS RAT

    EPA Science Inventory

    A PBPK model for TCE with specificity for the male LE rat that accurately predicts TCE tissue time-course data has not been developed, although other PBPK models for TCE exist. Development of such a model was the present aim. The PBPK model consisted of 5 compartments: fat; slowl...

  12. Vaginal thread formation in the healthy offspring of untreated Long-Evans rats

    EPA Science Inventory

    Vaginal threads are characterized as cords of mesenchymal tissue that cross the vaginal opening. They are sometimes apparent in rats after weaning, and typically disappear within 1-2 days as the female reaches puberty. If persistent, they can increase uncertainty in assessing rep...

  13. LATE GESTATIONAL ATRAZINE EXPOSURE DECREASES MATERNAL BEHAVIOR IN LONG-EVANS RATS

    EPA Science Inventory

    Late Gestational Atrazine Exposure Alters Maternal Nursing Behavior in Rats

    Jennifer L. Rayner1 and Suzanne E. Fenton2

    1 University of North Carolina at Chapel Hill, DESE, Chapel Hill, NC, and 2 USEPA/ ORD/NHEERL/Reproductive Toxicology Division, RTP, NC.

    At...

  14. Interactions between mecamylamine and alcohol in Long-Evans rats: flash-evoked potentials, body temperature, behavior, and blood alcohol concentration.

    PubMed

    Hetzler, Bruce E; Bauer, Alison M

    2013-06-01

    Mecamylamine, a noncompetitive antagonist of nicotinic acetylcholine receptors, has many potential clinical applications, including treating alcohol dependency. However, little is known about the combined effects of mecamylamine and alcohol on visual system electrophysiology. We examined the separate and combined effects of mecamylamine (4.0mg/kg, ip) and alcohol (2.0 g/kg, ip) on flash-evoked potentials (FEPs) recorded from the visual cortex (VC) and superior colliculus (SC) of chronically implanted adult male Long-Evans rats. On separate days, either saline or mecamylamine was given 10 min prior to either saline or ethanol. FEPs were recorded 15 and 30 min after the second injection. In the VC, alcohol significantly decreased the amplitudes of components P23, N29, N39, P89, N143, and P237, but increased P46. N63 amplitude was not significantly altered. In contrast, mecamylamine increased the amplitude of P23, P46, and N63, but reduced the amplitude of N29 and P237. The combination of mecamylamine and alcohol resulted in amplitudes very similar to alcohol alone for components P23, N29, N63, P89, N143, and P237. However, mecamylamine pretreatment reduced the effects of alcohol on components N39 and P46. In the SC, FEP component amplitudes were generally decreased by alcohol but not significantly altered by mecamylamine. Mecamylamine pretreatment did not significantly alter the effects of alcohol on SC amplitudes. Latencies of nearly all components in both structures were significantly increased by all drug treatments, with the greatest increase produced by the combination treatment. Hypothermia was also produced by all drug treatments, with the greatest hypothermia (2.25 °C) produced by the combination treatment, most likely accounting for much of the drug-induced increase in latencies. All drug treatments reduced movement during FEP testing, but later in an open field alcohol increased ambulation while mecamylamine reduced movement. Separate groups of

  15. Preventive effect of zinc compounds, polaprezinc and zinc acetate against the onset of hepatitis in Long-Evans Cinnamon rat.

    PubMed

    Sugawara, N; Katakura, M; Sugawara, C

    1999-02-01

    It is known that Long-Evans Cinnamon (LEC) rats are characterized by the fulminant hepatitis occurring as a result of an abnormal hepatic deposition of Cu due to the lack of the Cu-transporter p-type ATPase. To prevent the hepatitis, two Zn compounds, Zn acetate and polaprezinc were given orally to LEC rats aged 30 days. At 100 days after birth, the control group composed of LEC rats fed a basal diet (Cu, 17 ppm; Zn, 50 ppm; Fe, 150 ppm) exhibited slight jaundice and showed high activities of serum enzymes related to hepatic function. The groups fed the diet fortified (1000 ppm as Zn) with Zn acetate or polaprezinc did not have jaundice. The hepatic Cu concentrations were 174 +/- 34 micrograms/g and 156 +/- 23 micrograms/g in the polaplezinc group and Zn acetate group, respectively. The control group showed 267 +/- 17 micrograms Cu/g and 298 +/- 62 micrograms Fe/g in the liver. The Fe concentration was about 1.7 times the concentration in the two Zn groups. Hepatic free Cu and Fe concentrations were 2.6 +/- 0.3 and 21.4 +/- 5.8 micrograms/g, 1.7 +/- 0.7 and 6.8 +/- 1.1 micrograms/g, and 1.3 +/- 0.1 and 6.2 +/- 0.8 micrograms/g in the control, polaprezinc and zinc acetate groups, respectively. Intestinal metallothionein (MT) concentrations were not increased significantly by the Zn diets. The two Zn compounds inhibit Cu absorption from the intestinal tract, resulting in a decrease of hepatic Cu deposition. The new Zn compound as well as Zn acetate is categorized as a therapeutic drug for Cu poisoning, including Wilson's disease.

  16. Influence of gender on thermoregulation and cholinesterase inhibition in the long-evans rat exposed to diazinon.

    PubMed

    Gordon, Christopher J; Mack, Cina M

    2003-02-14

    Diazinon is an organophosphate (OP)-based, anticholinesterase insecticide that irreversibly inhibits acetylcholinesterase activity and produces cholinergic stimulation in central nervous system (CNS) and peripheral tissues. Our laboratory has found that OPs administered orally in rats induce a transient period of hypothermia followed by a delayed fever that persists for several days after exposure. There is little information on the thermoregulatory effects of diazinon. Core temperature (Tc) and motor activity (MA) were monitored by radiotelemetry in male and female rats of the Long-Evans strain dosed orally with diazinon (0 [corn-oil vehicle], 100, 200, or 300 mg/kg in males and 0, 50, 100, or 200 mg/kg in females). There was a dose-dependent decrease in Tc during the first night after treatment, with females exhibiting slightly greater sensitivity than males. MA was unaffected in females exposed to diazinon at doses of 50 to 200 mg/kg; MA of males was reduced during the first night after dosing with 300 mg/kg. There was a delayed elevation in Tc of males dosed with 200 and 300 mg/kg and females dosed with 50, 100, and 200 mg/kg diazinon. The elevated Tc was only manifested during d 2 and 3 after diazinon. Administration of 200 mg/kg sodium salicylate to females 48 h after being treated with 200 mg/kg diazinon led to a rapid abatement of the fever. Diazinon doses of 50 to 300 mg/kg led to 40% to 50% inhibition in plasma cholinesterase (ChE) activity 4 h after dosing, and females displayed a significantly slower recovery of ChE activity compared to males. When compared on a molar basis, the hypothermic response to diazinon was relatively small compared to other OPs such as chlorpyrifos. The delayed fever and efficacy of sodium salicylate to block diazinon-induced fever are similar to the effects of OPs chlorpyrifos and diisopropyl fluoro-phosphate (DFP). PMID:12521673

  17. Cessation of daily exercise dramatically alters precursors of hepatic steatosis in Otsuka Long-Evans Tokushima Fatty (OLETF) rats.

    PubMed

    Rector, R Scott; Thyfault, John P; Laye, Matthew J; Morris, R Tyler; Borengasser, Sarah J; Uptergrove, Grace M; Chakravarthy, Manu V; Booth, Frank W; Ibdah, Jamal A

    2008-09-01

    The purpose of this study was to delineate potential mechanisms initiating the onset of hepatic steatosis following the cessation of daily physical activity. Four-week-old, hyperphagic/obese Otsuka Long-Evans Tokushima Fatty rats were given access to voluntary running wheels for 16 weeks to prevent the development of hepatic steatosis. The animals were then suddenly transitioned to a sedentary condition as wheels were locked (wheel lock; WL) for 5 h (WL5), 53 h (WL53) or 173 h (WL173). Importantly after the cessation of daily exercise (5-173 h), no changes occurred in body weight, fat pad mass (omental and retroperitoneal), food intake, serum insulin, hepatic triglycerides or in the exercise-suppressed hepatic stearoyl-CoA desaturase-1 and peroxisome proliferator-activated receptor-gamma protein content. However, complete hepatic fatty acid oxidation and mitochondrial enzyme activities were highest at WL5 and WL53 and dropped significantly to SED levels by WL173. In addition, cessation of daily exercise quickly increased the hepatic protein contents of fatty acid synthase and acetyl-coenzyme A carboxylase (ACC), reduced ACC phosphorylation status, and dramatically increased hepatic malonyl-CoA concentration. This study is the first to show that the sudden cessation of daily exercise in a hyperphagic/obese model activates a subgroup of precursors and processes known to initiate hepatic steatosis, including decreased hepatic mitochondrial oxidative capacity, increased hepatic expression of de novo lipogenesis proteins, and increased hepatic malonyl CoA levels; each probably increasing the susceptibility to non-alcoholic fatty liver disease.

  18. Strain-dependent effects of acute caffeine on anxiety-related behavior in PVG/c, Long-Evans and Wistar rats.

    PubMed

    Hughes, Robert N; Hancock, Nicola J

    2016-01-01

    To assess the possibility that acute caffeine's behavioral action might depend on rats' strain, effects of 50mg/kg of the drug were observed on activity, anxiety-related behavior and habituation learning in male and female rats from three different strains, namely PVG/c, Long-Evans and Wistar. All subjects were tested in an open field, an elevated plus maze and a light-dark box. For the three strains combined, increased occupancy of the center of the open field and entries of the open plus-maze arms with caffeine suggested caffeine-induced anxiolysis, whereas increased grooming in the open field, decreased rearing in the plus maze and increased risk assessment in the light-dark box were consistent with anxiogenesis. Caffeine also reduced open-field rearing only for PVG/c rats, and entries into and occupation of the light side of the light-dark box only for Long-Evans rats, and increased total defecation in the three types of apparatus for all three strains combined. Overall, caffeine appeared to be mainly anxiogenic. The drug also increased open-field ambulation for PVG/c rats and walking for all rats, but decreased open-field ambulation and entries into the plus maze closed arms for Wistar rats alone. In general, Wistar rats appeared to be the least and Long-Evans the most anxious of the three strains investigated. Caffeine also decreased within-session habituation of open-field ambulation for PVG/c rats alone, thereby suggesting strain-dependent interference with non-associative learning and short-term memory. Several overall sex differences were also observed that supported female rats being more active and less anxious than males.

  19. Strain-dependent effects of acute caffeine on anxiety-related behavior in PVG/c, Long-Evans and Wistar rats.

    PubMed

    Hughes, Robert N; Hancock, Nicola J

    2016-01-01

    To assess the possibility that acute caffeine's behavioral action might depend on rats' strain, effects of 50mg/kg of the drug were observed on activity, anxiety-related behavior and habituation learning in male and female rats from three different strains, namely PVG/c, Long-Evans and Wistar. All subjects were tested in an open field, an elevated plus maze and a light-dark box. For the three strains combined, increased occupancy of the center of the open field and entries of the open plus-maze arms with caffeine suggested caffeine-induced anxiolysis, whereas increased grooming in the open field, decreased rearing in the plus maze and increased risk assessment in the light-dark box were consistent with anxiogenesis. Caffeine also reduced open-field rearing only for PVG/c rats, and entries into and occupation of the light side of the light-dark box only for Long-Evans rats, and increased total defecation in the three types of apparatus for all three strains combined. Overall, caffeine appeared to be mainly anxiogenic. The drug also increased open-field ambulation for PVG/c rats and walking for all rats, but decreased open-field ambulation and entries into the plus maze closed arms for Wistar rats alone. In general, Wistar rats appeared to be the least and Long-Evans the most anxious of the three strains investigated. Caffeine also decreased within-session habituation of open-field ambulation for PVG/c rats alone, thereby suggesting strain-dependent interference with non-associative learning and short-term memory. Several overall sex differences were also observed that supported female rats being more active and less anxious than males. PMID:26577750

  20. Development of an inhalation physiologically based pharmacokinetic (PBPK) model for 2,2, 4-trimethylpentane (TMP) in male Long-Evans rats using gas uptake experiments.

    PubMed

    El-Masri, Hisham A; Dowd, Sean; Pegram, Rex A; Harrison, Randy; Yavanhxay, Sisouphanh J; Simmons, Jane Ellen; Evans, Marina

    2009-12-01

    2,2,4-Trimethylpentane (TMP) is a volatile colorless liquid used primarily to increase the octane rating of combustible fuels. TMP is released in the environment through the manufacture, use, and disposal of products associated with the gasoline and petroleum industry. Short-term inhalation exposure to TMP (< 4 h; > 1000 ppm) caused sensory and motor irritations in rats and mice. Like many volatile hydrocarbons, acute exposure to TMP may also be expected to alter neurological functions. To estimate in vivo metabolic kinetics of TMP and to predict its target tissue dosimetry during inhalation exposures, a physiologically based pharmacokinetic (PBPK) model was developed for the chemical in Long-Evans male rats using closed-chamber gas-uptake experiments. Gas-uptake experiments were conducted in which rats (80-90 days old) were exposed to targeted initial TMP concentrations of 50, 100, 500, and 1000 ppm. The model consisted of compartments for the closed uptake chamber, lung, fat, kidney, liver, brain, and rapidly and slowly perfused tissues. Physiological parameters were obtained from literature. Partition coefficients for the model were experimentally determined for air/blood, fat, liver, kidney, muscle, and brain using vial equilibration methods. Common to other hydrocarbons, metabolism of TMP via oxidative reactions is assumed to mainly occur in the liver. The PBPK model simulations of the closed chamber data were used to estimate in vivo metabolic parameters for TMP in male Long-Evans rats.

  1. Rare sugar D-psicose improves insulin sensitivity and glucose tolerance in type 2 diabetes Otsuka Long-Evans Tokushima Fatty (OLETF) rats.

    PubMed

    Hossain, Mohammad A; Kitagaki, Shigeru; Nakano, Daisuke; Nishiyama, Akira; Funamoto, Yasunobu; Matsunaga, Toru; Tsukamoto, Ikuko; Yamaguchi, Fuminori; Kamitori, Kazuyo; Dong, Youyi; Hirata, Yuko; Murao, Koji; Toyoda, Yukiyasu; Tokuda, Masaaki

    2011-02-01

    A rare sugar, D-psicose has progressively been evaluated as a unique metabolic regulator of glucose and lipid metabolism, and thus represents a promising compound for the treatment of type 2 diabetes mellitus (T2DM). The present study was undertaken to examine the underlying effector organs of D-psicose in lowering blood glucose and abdominal fat by exploiting a T2DM rat model, Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Rats were fed 5% D-psicose or 5% D-glucose supplemented in drinking water, and only water in the control for 13 weeks and the protective effects were compared. A non-diabetic Long-Evans Tokushima Otsuka (LETO), fed with water served as a counter control of OLETF. After 13 weeks feeding, D-psicose treatment significantly reduced the increase in body weight and abdominal fat mass. Oral glucose tolerance test (OGTT) showed the reduced blood glucose and insulin levels suggesting the improvement of insulin resistance in OLETF rats. Oil-red-O staining elucidated that D-psicose significantly reduced lipid accumulation in the liver. Immunohistochemical analysis showed D-psicose induced glucokinase translocation from nucleus to cytoplasm of the liver which enhances glucokinase activity and subsequent synthesis of glycogen in the liver. D-psicose also protected the pathological change of the β-cells of pancreatic islets. These data demonstrate that D-psicose controls blood glucose levels by reducing lipotoxicity in liver and by preserving pancreatic β-cell function.

  2. Nicotine and ethanol co-use in Long-Evans rats: Stimulatory effects of perinatal exposure to a fat-rich diet.

    PubMed

    Karatayev, Olga; Lukatskaya, Olga; Moon, Sang-Ho; Guo, Wei-Ran; Chen, Dan; Algava, Diane; Abedi, Susan; Leibowitz, Sarah F

    2015-08-01

    Clinical studies demonstrate frequent co-existence of nicotine and alcohol abuse and suggest that this may result, in part, from the ready access to and intake of fat-rich diets. Whereas animal studies show that high-fat diet intake in adults can enhance the consumption of either nicotine or ethanol and that maternal consumption of a fat-rich diet during pregnancy increases operant responding for nicotine in offspring, little is known about the impact of dietary fat on the co-abuse of these two drugs. The goal of this study was to test in Long-Evans rats the effects of perinatal exposure to fat on the co-use of nicotine and ethanol, using a novel paradigm that involves simultaneous intravenous (IV) self-administration of these two drugs. Fat- vs. chow-exposed offspring were characterized and compared, first in terms of their nicotine self-administration behavior, then in terms of their nicotine/ethanol self-administration behavior, and lastly in terms of their self-administration of ethanol in the absence of nicotine. The results demonstrate that maternal consumption of fat compared to low-fat chow during gestation and lactation significantly stimulates nicotine self-administration during fixed-ratio testing. It also increases nicotine/ethanol self-administration during fixed-ratio and dose-response testing, with BEC elevated to 120 mg/dL, and causes an increase in breakpoint during progressive ratio testing. Of particular note is the finding that rats perinatally exposed to fat self-administer significantly more of the nicotine/ethanol mixture as compared to nicotine alone, an effect not evident in the chow-control rats. After removal of nicotine from the nicotine/ethanol mixture, this difference between the fat- and chow-exposed rats was lost, with both groups failing to acquire the self-administration of ethanol alone. Together, these findings suggest that perinatal exposure to a fat-rich diet, in addition to stimulating self-administration of nicotine, causes

  3. Nicotine and ethanol co-use in Long-Evans rats: Stimulatory effects of perinatal exposure to a fat-rich diet

    PubMed Central

    Karatayev, Olga; Lukatskaya, Olga; Moon, Sang-Ho; Guo, Wei-Ran; Chen, Dan; Algava, Diane; Abedi, Susan; Leibowitz, Sarah F.

    2015-01-01

    Clinical studies demonstrate frequent co-existence of nicotine and alcohol abuse and suggest that this may result, in part, from the ready access to and intake of fat-rich diets. Whereas animal studies show that high-fat diet intake in adults can enhance the consumption of either nicotine or ethanol and that maternal consumption of a fat-rich diet during pregnancy increases operant responding for nicotine in offspring, little is known about the impact of dietary fat on the co-abuse of these two drugs. The goal of this study was to test in Long-Evans rats the effects of perinatal exposure to fat on the co-use of nicotine and ethanol, using a novel paradigm that involves simultaneous intravenous (IV) self-administration of these two drugs. Fat- vs. chow-exposed offspring were characterized and compared, first in terms of their nicotine self-administration behavior, then in terms of their nicotine/ethanol self-administration behavior, and lastly in terms of their self-administration of ethanol in the absence of nicotine. The results demonstrate that maternal consumption of fat compared to low-fat chow during gestation and lactation significantly stimulates nicotine self-administration during fixed-ratio testing. It also increases nicotine/ethanol self-administration during fixed-ratio and dose-response testing, with BEC elevated to 120 mg/dL, and causes an increase in breakpoint during progressive ratio testing. Of particular note is the finding that rats perinatally exposed to fat self-administer significantly more of the nicotine/ethanol mixture as compared to nicotine alone, an effect not evident in the chow-control rats. After removal of nicotine from the nicotine/ethanol mixture, this difference between the fat- and chow-exposed rats was lost, with both groups failing to acquire the self-administration of ethanol alone. Together, these findings suggest that perinatal exposure to a fat-rich diet, in addition to stimulating self-administration of nicotine, causes

  4. ATRAZINE-INDUCED REPRODUCTIVE TRACT ALTERATIONS AFTER TRANSPLACENTAL AND LACTATIONAL EXPOSURE IN LONG-EVANS RAT PUPS

    EPA Science Inventory

    Studies have shown that early postnatal exposure to the common herbicide atrazine (ATR) will delay preputial separation (PPS) in Wistar rats and increase incidence of prostate inflammation in adults. To evaluate ATR exposure parameters required for pubertal delays (PPS), we used...

  5. ATRAZINE-INDUCED REPRODUCTIVE TRACT ALTERATIONS AFTER TRANSPLACENTAL AND LACTATIONAL EXPOSURE IN MALE LONG-EVANS RATS.

    EPA Science Inventory

    Studies showed that early postnatal exposure to the herbicide atrazine (ATR) delayed preputial separation (PPS) and increased incidence of prostate inflammation in adult Wistar rats. A cross-fostering paradigm was used in this study to determine if gestational exposure to ATR wou...

  6. Role of p38 Mapk in development of acute hepatic injury in Long-Evans Cinnamon (LEC) rats, an animal model of human Wilson's disease.

    PubMed

    Kadowaki, Shingo; Meguro, Saori; Imaizumi, Yoshitaka; Sakai, Hiroshi; Endoh, Daiji; Hayashi, Masanobu

    2013-12-30

    The Long-Evans Cinnamon (LEC) rat, an animal model of human Wilson's disease, spontaneously develops fulminant hepatitis associated with severe jaundice at about 4 months of age. In this study, we examined the changes in gene expression during progression of acute hepatic injury. When levels of gene expression in the liver of LEC rats at 13 weeks of age were compared to those in rats at 4 weeks of age using oligonucleotide arrays, 1,620 genes out of 7,700 genes analyzed showed more than 2-fold differences. Expression levels of 11 of 29 genes related to stress-activating protein kinase (SAPK) changed by more than 2-fold in the liver of LEC rats, but none of the SAPK-related genes showed changes in expression levels in the liver of control rats. Activity of p38 mapk in the liver of LEC rats at 13 weeks of age was about 8.1-fold higher than that in rats at 4 weeks of age. When LEC rats were administered SB203580, a p38 mapk-specific inhibitor, by s.c. injection twice a week from 10 to 13 weeks of age, activities of p38 mapk in the liver, activities of AST and ALT and concentrations of bilirubin in sera of rats administered SB203580 significantly decreased compared to those in rats not administered. These results showed that the increase in activities of p38 mapk was related to the occurrence of acute hepatic injury in LEC rats.

  7. Inhibition of hereditary hepatitis and liver tumor development in Long-Evans cinnamon rats by the copper-chelating agent trientine dihydrochloride.

    PubMed

    Sone, K; Maeda, M; Wakabayashi, K; Takeichi, N; Mori, M; Sugimura, T; Nagao, M

    1996-04-01

    Trientine dihydrochloride (trientine) is an alternative medicinal copper chelating agent for patients with Wilson's disease of penicillamine intolerance. We examined the effects of trientine on the spontaneous development of hepatitis and hepatic tumors, by its short-term and long-term administration to Long-Evans cinnamon (LEC) rats with an accumulation of copper in the liver, as animal models of Wilson's disease. Male rats were given trientine in their drinking water at 1500 ppm for 18 weeks, from 6 weeks to 24 weeks of age in short-term experiment, and 1500 ppm for 27 weeks then 750 ppm for 52 weeks, from 8 to 87 weeks of age in the long-term experiment. Development of hepatitis was observed in the control LEC rats at 18 weeks of age. They had high levels of plasma transaminases (glutamic oxaloacetic transaminase [GOT], glutamic pyruvic transaminase [GPT]), and on pathological examination, hepatocyte destruction was observed. Histological findings revealed that short-term administration of trientine inhibited the development of hepatitis remarkably. The plasma GOT and GPT levels of treated animals were only slightly higher than those of normal LEA (Long-Evans with agouti coat color) rats, a sibling line of LEC rats. Copper levels in the liver were decreased by a maximum of 50 percent. In the long-term administration of trientine, the incidence of hepatic cell carcinoma (HCC) in the treated rats was 67 percent that of the untreated LEC rats, and the number of HCCs per rat in the treated group was 0.7 +/- 0.5, being significantly lower as compared with 4.7 +/- 3.5 in the untreated rats. Additionally, the development of cholangiofibrosis in LEC rats was completely prevented by long-term administration of the agent. The copper level in the liver of treated rats was reduced by 33 percent at 87 weeks of age. Development of HCC in LEC rats might be partly, but not totally, because of copper accumulation. No effects on the levels of copper, iron, or zinc in the liver of

  8. Therapeutic effects of tetrathiomolybdate on hepatic dysfunction occurring naturally in Long-Evans Cinnamon (LEC) rats: a bona fide animal model for Wilson's disease.

    PubMed

    Sugawara, N; Lai, Y R; Sugawara, C

    1999-02-01

    Long-Evans Cinnamon (LEC) rats were fed a diet containing 7 ppm Cu and 30 ppm Cu from 60 days after birth. Fischer (Fischer group) and LEC (LEC-control group) rats fed a 7 ppm Cu diet showed normal growth throughout the whole period (60 to 125 days after birth). On the other hand, LEC rats fed the 30 ppm Cu diet had decreased body weight and showed slight jaundice at around 100 days after birth. Tetrathiomolybdate (TTM, 10 mg/kg bw) was injected sub-cutaneously at 101 and 105 days after birth into half of the LEC rats fed the 30 ppm Cu diet. LEC rats given TTM (LEC+TTM group) recovered their body weight and the jaundice rapidly disappeared. However, LEC rats without TTM (LEC-TTM group) had sharply decreased body weight and showed severe jaundice at 103 days after birth. The hepatic Cu concentration in LEC+TTM rats (460 micrograms/g) exceeded that of LEC-control rats (330 micrograms/g) at 125 days after birth. Our data suggest that TTM is effective for treatment of acute hepatic injury in the LEC rat.

  9. Inhibitory effects of trientine, a copper-chelating agent, on induction of DNA strand breaks in kidney cells of Long-Evans Cinnamon (LEC) rats.

    PubMed

    Hayashi, Masanobu; Miyane, Kazuhiro; Senou, Misato; Endoh, Daiji; Higuchi, Hidetoshi; Nagahata, Hajime; Nakayama, Kenji; Kon, Yasuhiro; Okui, Toyo

    2005-10-01

    The effects of treatment with trientine, a specific copper-chelating agent, on the accumulation of copper and induction of DNA strand breaks were investigated in Long-Evans Cinnamon (LEC) rats, an animal model for human Wilson's disease. Copper accumulated in the kidneys of LEC rats in an age-dependent manner from 12 to 18 weeks of age. When LEC rats were treated with trientine from 10 weeks of age, renal copper contents did not increase and were maintained at the same levels as those in 4-week-old LEC rats. Estimation of the amounts of DNA single-strand breaks (SSBs) by comet assay showed that SSBs of DNA were induced in a substantial population of LEC rat renal cortex cells around 12 weeks of age and that the amounts of SSBs increased in an age-dependent manner from 12 to 18 weeks of age. When LEC rats were treated with trientine from 10 weeks of age, the observed number of cells with DNA damage decreased, suggesting that induction of SSBs of DNA was inhibited and/or SSBs were repaired during the period of treatment with trientine. The results show that SSBs of DNA in LEC rat kidney cells are induced prior to occurrence of clinical signs of hepatic injury and that treatment of LEC rats with trientine decreases the number of DNA strand breaks.

  10. Comparison of the enhancement of plasma glucose levels in type 2 diabetes Otsuka Long-Evans Tokushima Fatty rats by oral administration of sucrose or maple syrup.

    PubMed

    Nagai, Noriaki; Ito, Yoshimasa; Taga, Atsushi

    2013-01-01

    Maple syrup is used as a premium natural sweeter, and is known for being good for human health. In the present study, we investigate whether maple syrup is suitable as a sweetener in the management of type 2 diabetes using Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes mellitus. OLETF rats develop type 2 diabetes mellitus by 30 weeks of age, and 60-week-old OLETF rats show hyperglycemia and hypoinsulinemia via pancreatic β-cell dysfunction. The administration of sucrose or maple syrup following an OGT test increased plasma glucose (PG) levels in OLETF rats, but the enhancement in PG following the oral administration of maple syrup was lower than in the case of sucrose administration in both 30- and 60-week-old OLETF rats. Although, the insulin levels in 30-week-old OLETF rats also increased following the oral administration of sucrose or maple syrup, no increase in insulin levels was seen in 60-week-old OLETF rats following the oral administration of either sucrose or maple syrup. No significant differences were observed in insulin levels between sucrose- and maple syrup-administered OLETF rats at either 30 or 60 weeks of age. The present study strongly suggests that the maple syrup may have a lower glycemic index than sucrose, which may help in the prevention of type 2 diabetes.

  11. Inhibitory effects of trientine, a copper-chelating agent, on induction of DNA strand breaks in hepatic cells of Long-Evans Cinnamon rats.

    PubMed

    Hayashi, Masanobu; Miyane, Kazuhiro; Hirooka, Takeshi; Endoh, Daiji; Higuchi, Hidetoshi; Nagahata, Hajime; Nakayama, Kenji; Kon, Yashuhiro; Okui, Toyo

    2004-11-01

    Effects of treatment with trientine, a specific copper-chelating agent, on accumulation of copper and induction of DNA strand breaks were investigated in Long-Evans Cinnamon (LEC) rats, an animal model for human Wilson's disease. Copper accumulated in the livers of LEC rats in an age-dependent manner from 4 to 13 weeks of age. When LEC rats were treated with trientine from 10 weeks of age, hepatic copper contents did not increase and were maintained at the same levels as those in 10-week-old LEC rats. When the amounts of DNA single-strand breaks (SSBs) were estimated by a comet assay, SSBs of DNA were induced in a substantial population of LEC rat hepatic cells around 8 weeks of age and the amounts of SSBs increased in an age-dependent manner from 8 to 15 weeks of age. When LEC rats were treated with trientine from 10 weeks of age, the observed number of cells with DNA damage decreased dramatically, suggesting that induction of SSBs of DNA was inhibited and/or SSBs were repaired during the period of treatment with trientine. The results show that treatment of LEC rats with trientine decreases the number of DNA strand breaks observed, although copper contents remain high in the liver.

  12. Inhibitory effects of fermented brown rice and rice bran on the development of acute hepatitis in Long-Evans Cinnamon rats.

    PubMed

    Shibata, Toshiyuki; Nagayasu, Hiroki; Kitajo, Hiroyuki; Arisue, Makoto; Yamashita, Tomomi; Hatakeyama, Daijiro; Iwasaki, Teruaki; Kobayashi, Hiroshi

    2006-04-01

    To investigate the effects of fermented brown rice (FBRA) on the development of hereditary hepatitis in Long-Evans Cinnamon (LEC) rats, we compared the incidence and grades of acute hepatitis among rats fed 5% and 10% FBRA in the conventional diet and the conventional diet alone. Both the 5% and 10% FBRA-supplemented diets indicated a tendency to prevent the development of hepatitis, and the significant effect of 10% FBRA was observed until 16-17 weeks of age in the accumulated incidence and survival ratio compared with the unsupplemented conventional diet, although no significant difference was observed between 5% and 10% FBRA-supplemented diets. At the age of 12 weeks, which is just before the rats develop hepatitis, serum copper levels in rats fed either of the test diets were similar to those in rats fed the conventional diet. Furthermore, the copper concentration in liver tissue at 12 weeks of age was not changed by the test diet. These results suggest that FBRA has preventive effects on the development of hepatitis in LEC rats and may play an important role in protecting the liver against the free radicals induced by copper accumulation in the liver.

  13. Protection from spontaneous hepatocellular damage by N-benzyl-d-glucamine dithiocarbamate in Long-Evans Cinnamon rats, an animal model of Wilson's disease.

    PubMed

    Shimada, Hideaki; Takahashi, Makiko; Shimada, Akinori; Okawara, Tadashi; Yasutake, Akira; Imamura, Yorishige; Kiyozumi, Morio

    2005-01-01

    The Long-Evans Cinnamon (LEC) rat is a mutant strain that accumulates excessive tissue copper (Cu) and models the clinical symptoms and biological features of Wilson's disease in humans. We compared the effects of three metal chelating agents, N-benzyl-d-glucamine dithiocarbamate (BGD), d-penicillamine (D-PEN), and triethylenetetramine (TETA), on the biliary and urinary excretions of Cu using LEC rats. The animals were treated ip with each chelating agent (1 mmol/kg body weight) and then the bile and urine samples were collected for 3 h. Because single treatment with BGD markedly stimulated biliary excretion of Cu, the protective effect of repeated BGD injection on spontaneous hepatocellular damage was further examined. Separate groups received two weekly injections of BGD starting at 11 weeks of age and were compared to saline-injected controls. Serum alanine aminotransferase (ALT) activity and bilirubin level were significantly increased in control LEC rats by 19 weeks of age and histopathological analysis demonstrated extensive hepatic damage in these rats. However, repeated BGD injections prevented the increases in serum ALT and bilirubin and blocked the histopathological changes in the liver. Furthermore, although Cu rapidly accumulated in the liver, kidney, spleen, and serum of control LEC rats during the test period, repeated BGD injection largely prevented these increases. These results indicate that BGD treatment is effective in blocking excessive Cu accumulation in LEC rats that, in turn, provides protection from spontaneous liver damage.

  14. Characterization of spatial performance in male and female Long-Evans rats by means of the Morris water task and the ziggurat task.

    PubMed

    Faraji, Jamshid; Metz, Gerlinde A; Sutherland, Robert J

    2010-01-15

    Sex differences are prominent influences on spatial performance. One of the most common tasks to assess sex differences in spatial navigation in rodents is the Morris water task (MWT). In this task rats swim in a pool of water to locate a hidden platform employing the topographical relationships among the distal visual cues, pool wall, and goal location. Some evidence suggests that male rats display superior performance relative to females in the MWT. It is unknown, however, to what extent the sex difference in rats is task-dependent. This study compared the performance of male and female Long-Evans rats in the wet-land MWT versus the dry-land ziggurat task (ZT). The ZT represents a new dry-land task in which rats explore an arena with 16 ziggurat pyramids to locate food rewards. Several behavioural parameters, including latency, path length, path speed, probe trial performance, errors, and the number of returns were used as indices of spatial learning and memory. While males and females did not display significant differences in the traditional measures of spatial navigation within MWT, they displayed a robust sex difference in all measures of the ZT. These results indicate task-specific sex differences in spatial performance. Our findings suggest that males and females may employ different learning strategies in the MWT and ZT and that the latter task provides a more favourable task for assessing sex differences in rats.

  15. Rare sugar d-psicose prevents progression and development of diabetes in T2DM model Otsuka Long-Evans Tokushima Fatty rats

    PubMed Central

    Hossain, Akram; Yamaguchi, Fuminori; Hirose, Kayoko; Matsunaga, Toru; Sui, Li; Hirata, Yuko; Noguchi, Chisato; Katagi, Ayako; Kamitori, Kazuyo; Dong, Youyi; Tsukamoto, Ikuko; Tokuda, Masaaki

    2015-01-01

    Background The fundamental cause of overweight and obesity is consumption of calorie-dense foods. We have introduced a zero-calorie sweet sugar, d-psicose (d-allulose), a rare sugar that has been proven to have strong antihyperglycemic and antihyperlipidemic effects, and could be used as a replacement of natural sugar for the obese and diabetic subjects. Aim Above mentioned efficacy of d-psicose (d-allulose) has been confirmed in our previous studies on type 2 diabetes mellitus (T2DM) model Otsuka Long-Evans Tokushima Fatty (OLETF) rats with short-term treatment. In this study we investigated the long-term effect of d-psicose in preventing the commencement and progression of T2DM with the mechanism of preservation of pancreatic β-cells in OLETF rats. Methods Treated OLETF rats were fed 5% d-psicose dissolved in water and control rats only water. Nondiabetic control rats, Long-Evans Tokushima Otsuka (LETO), were taken as healthy control and fed water. To follow the progression of diabetes, periodic measurements of blood glucose, plasma insulin, and body weight changes were continued till sacrifice at 60 weeks. Periodic in vivo body fat mass was measured. On sacrifice, pancreas, liver, and abdominal adipose tissues were collected for various staining tests. Results d-Psicose prevented the commencement and progression of T2DM till 60 weeks through the maintenance of blood glucose levels, decrease in body weight gain, and the control of postprandial hyperglycemia, with decreased levels of HbA1c in comparison to nontreated control rats. This improvement in glycemic control was accompanied by the maintenance of plasma insulin levels and the preservation of pancreatic β-cells with the significant reduction in inflammatory markers. Body fat accumulation was significantly lower in the treatment group, with decreased infiltration of macrophages in the abdominal adipose tissue. Conclusion Our findings suggest that the rare sugar d-psicose could be beneficial for the

  16. Effect of magnesium ion supplementation on obesity and diabetes mellitus in Otsuka Long-Evans Tokushima Fatty (OLETF) rats under excessive food intake.

    PubMed

    Nagai, Noriaki; Ito, Yoshimasa

    2013-01-01

    Several epidemiologic studies have found that magnesium ion (Mg²⁺) is related to obesity and type 2 diabetes mellitus. However, there have been almost no reports on the effects of a combination of excessive food intake and Mg²⁺ supplementation on metabolic syndrome and various blood tests values for diabetes mellitus. In this study, we investigated changes in body weight and blood test values for diabetes mellitus of Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model for human type 2 diabetes mellitus via metabolic syndrome, under conditions of combined excessive food intake and Mg²⁺ supplementation. The rats received Mg²⁺ supplementation by drinking magnesium water (Mg²⁺; 200 mg/l). No significant differences were observed in the levels of food or water intake between OLETF rats drinking purified water (PW) or magnesium water (MW). Type 2 diabetes mellitus with metabolic syndrome developed at 30 weeks of age, and the body weights and plasma insulin levels of OLETF rats at 60 weeks of age were lower than those of normal rats. The plasma glucose (PG) levels in 38-week-old OLETF rats drinking MW were significantly lower than in those of rats drinking PW, while the body weights and the levels of triglycerides (TG) and insulin of 38-week-old MW-drinking OLETF rats were significantly higher than those of their PW-drinking counterparts. On the other hand, the decreases in body weight and insulin levels in 60-week-old OLETF rats were suppressed by MW supplementation. The present study demonstrates that Mg²⁺ supplementation delays the development of diabetes mellitus in OLETF rats under conditions of excessive food intake. In addition, obesity and high blood TG levels were observed in OLETF rats receiving Mg²⁺ supplementation in conjunction with excessive food intake.

  17. The effect of subcutaneous tetrathiomolybdate administration on copper and iron metabolism, including their regional redistribution in the brain, in the Long-Evans Cinnamon rat, a bona fide animal model for Wilson's disease.

    PubMed

    Sugawara, N; Ikeda, T; Lai, Y R; Sugawara, C

    1999-05-01

    The present work was performed to examine the effect of tetrathiomolybdate on Cu and Fe metabolism, especially redistribution of Cu and Fe in the brains of Long-Evans Cinnamon rats, with inherently abnormal Cu deposition in the liver. The drug was injected subcutaneously at 5 mg/kg of body weight twice a week for 65 days (total dose of 20 mg) into 40-day-old Long-Evans Cinnamon rats. In Long-Evans Cinnamon rats treated with tetrathiomolybdate, the hepatic Cu concentration was 60 microg/g wet weight, compared to 170 microg/g in untreated rats. In seven brain regions (cerebellum, medulla oblongata, hypothalamus, striatum, midbrain, hippocampus and cortex) of the Long-Evans Cinnamon rats treated with tetrathiomolybdate. the Cu concentration (1.5 to 2.3 microg/g) was slightly lower (1.6 to 2.7 microg/g) than in untreated rats. A significant difference between the two groups was found only in the midbrain. Brain Fe concentrations in regions other than the striatum were not changed significantly by the tetrathiomolybdate injections. The hepatic Fe concentration was about 120 microg/g in Long-Evans Cinnamon rats without tetrathiomolybdate. Tetrathiomolybdate injection further increased the concentration to about 250 microg/g. Our results indicated that subcutaneous tetrathiomolybdate injection did not have an effect that stimulated redistribution of Cu and Fe in the seven brain regions examined, although hepatic Cu was markedly decreased and the removed Cu was deposited in kidneys, spleen and testes. The increased hepatic Fe level should be taken into account when considering side effects of the compound.

  18. Taurine ameliorates hyperglycemia and dyslipidemia by reducing insulin resistance and leptin level in Otsuka Long-Evans Tokushima fatty (OLETF) rats with long-term diabetes

    PubMed Central

    Oh, Da Hee; Kim, Jung Yeon; Lee, Bong Gn; You, Jeong Soon; Chang, Kyung Ja; Chung, Hyunju; Yoo, Myung Chul; Yang, Hyung-In; Kang, Ja-Heon; Hwang, Yoo Chul; Ahn, Kue Jeong; Chung, Ho-Yeon

    2012-01-01

    This study aimed to determine whether taurine supplementation improves metabolic disturbances and diabetic complications in an animal model for type 2 diabetes. We investigated whether taurine has therapeutic effects on glucose metabolism, lipid metabolism, and diabetic complications in Otsuka Long-Evans Tokushima fatty (OLETF) rats with long-term duration of diabetes. Fourteen 50-week-old OLETF rats with chronic diabetes were fed a diet supplemented with taurine (2%) or a non-supplemented control diet for 12 weeks. Taurine reduced blood glucose levels over 12 weeks, and improved OGTT outcomes at 6 weeks after taurine supplementation, in OLETF rats. Taurine significantly reduced insulin resistance but did not improve β-cell function or islet mass. After 12 weeks, taurine significantly decreased serum levels of lipids such as triglyceride, cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol. Taurine significantly reduced serum leptin, but not adiponectin levels. However, taurine had no therapeutic effect on damaged tissues. Taurine ameliorated hyperglycemia and dyslipidemia, at least in part, by improving insulin sensitivity and leptin modulation in OLETF rats with long-term diabetes. Additional study is needed to investigate whether taurine has the same beneficial effects in human diabetic patients. PMID:23114424

  19. Effects of prenatal exposure to a low dose atrazine metabolite mixture on pubertal timing and prostate development of male Long-Evans rats.

    PubMed

    Stanko, Jason P; Enoch, Rolondo R; Rayner, Jennifer L; Davis, Christine C; Wolf, Douglas C; Malarkey, David E; Fenton, Suzanne E

    2010-12-01

    The present study examines the postnatal reproductive development of male rats following prenatal exposure to an atrazine metabolite mixture (AMM) consisting of the herbicide atrazine and its environmental metabolites diaminochlorotriazine, hydroxyatrazine, deethylatrazine, and deisopropylatrazine. Pregnant Long-Evans rats were treated by gavage with 0.09, 0.87, or 8.73mg AMM/kg body weight (BW), vehicle, or 100mg ATR/kg BW positive control, on gestation days 15-19. Preputial separation was significantly delayed in 0.87 mg and 8.73mg AMM-exposed males. AMM-exposed males demonstrated a significant treatment-related increase in incidence and severity of inflammation in the prostate on postnatal day (PND) 120. A dose-dependent increase in epididymal fat masses and prostate foci were grossly visible in AMM-exposed offspring. These results indicate that a short, late prenatal exposure to mixture of chlorotriazine metabolites can cause chronic prostatitis in male LE rats. The mode of action for these effects is presently unclear.

  20. Investigation of DNA synthesis in experimentally induced Long-Evans rat myeloschisis by the BrdU/antiBrdU technique.

    PubMed

    Chono, Y; Abe, H; Iwasaki, Y; Nagashima, K

    1994-04-01

    The volume and DNA synthesis of the neuroepithelium in induced myeloschisis in Long-Evans rats as shown by hematoxylin-eosin and BrdU/antiBrdU immunohistochemical staining patterns were examined at different stages of embryonal development. On day 14 of gestation, control animals contained BrdU-incorporating cells mainly at the alar plate of the closed neural tube. On the same day, the everted neural plate of rats with myeloschisis showed active, diffuse uptake of BrdU in the cells of the matrix layer, although an increase in the volume of the everted neural plate was not yet identifiable. On day 21 of gestation, rats with myeloschisis showed a marked increase in the volume of the neuroepithelium compared with controls. Our investigations suggest that, in myeloschisis, more neuroepithelial cells than normal retain their capability for DNA synthesis on day 14 of gestation, and the overgrowth of the neuroepithelium found on day 21 is possibly a secondary effect of failure of neural tube closure.

  1. Regional cerebral incorporation of plasma (/sup 14/C)palmitate, and cerebral glucose utilization, in water-deprived Long-Evans and Brattleboro rats

    SciTech Connect

    Noronha, J.G.; Larson, D.M.; Rapoport, S.I.

    1989-03-01

    Regional rates of incorporation into brain of intravenously administered (/sup 14/C)palmitate and regional cerebral metabolic rates for glucose (rCMRglc) were measured in water-provided (WP) and water-deprived (WD) homozygous (DI) and heterozygous (HZ) Brattleboro rats, a mutant strain unable to synthesize vasopressin, and in the parent Long-Evans (LE) strain. Following 15 h or 4 days of water deprivation, rCMRglc was elevated threefold in the pituitary neural lobe of LE-WD and DI-WD as compared with LE-WP rats, and in the paraventricular nucleus of LE-WD, and the supraoptic nucleus of DI-WD rats. However, incorporation of (/sup 14/C)palmitate into these regions was not specifically altered. The results indicate that water deprivation for up to 4 days increases rCMRglc in some brain regions involved with vasopressin, but does not alter (/sup 14/C)palmitate incorporation into these regions. Incorporation of plasma (/sup 14/C)palmitate is independent of unlabeled plasma palmitate at brain regions which have an intact blood-brain barrier, but at nonbarrier regions falls according to saturation kinetics as cold plasma concentration rises, with a mean half-saturation constant (Km) equal to 0.136 mumol.ml-1.

  2. Effects of prenatal exposure to a low dose atrazine metabolite mixture on pubertal timing and prostate development of male Long-Evans rats

    SciTech Connect

    Stanko, Jason; Enoch, Rolondo; Rayner, Jennifer L; Davis, Christine; Wolf, Douglas; Malarkey, David; Fenton, Suzanne

    2010-12-01

    The present study examines the postnatal reproductive development of male rats following prenatal exposure to an atrazine metabolite mixture (AMM) consisting of the herbicide atrazine and its environmental metabolites diaminochlorotriazine, hydroxyatrazine, deethylatrazine, and deisopropylatrazine. Pregnant Long-Evans rats were treated by gavage with 0.09, 0.87, or 8.73 mg AMM/kg body weight (BW), vehicle, or 100 mg ATR/kg BW positive control, on gestation days 15 19. Preputial separation was significantly delayed in 0.87 mg and 8.73 mg AMM-exposed males. AMM-exposed males demonstrated a significant treatment-related increase in incidence and severity of inflammation in the prostate on postnatal day (PND) 120. A dose-dependent increase in epididymal fat masses and prostate foci were grossly visible in AMM-exposed offspring. These results indicate that a short, late prenatal exposure to mixture of chlorotriazine metabolites can cause chronic prostatitis in male LE rats. The mode of action for these effects is presently unclear.

  3. Effects of Prenatal Exposure to a Low Dose Atrazine Metabolite Mixture on Pubertal Timing and Prostate Development of Male Long Evans Rats

    PubMed Central

    Stanko, Jason P.; Enoch, Rolondo R.; Rayner, Jennifer L.; Davis, Christine C.; Wolf, Douglas C.; Malarkey, David E.; Fenton, Suzanne E.

    2010-01-01

    The present study examines the postnatal reproductive development of male rats following prenatal exposure to an atrazine metabolite mixture (AMM) consisting of the herbicide atrazine and its environmental metabolites diaminochlorotriazine, hydroxyatrazine, deethylatrazine, and deisopropylatrazine. Pregnant Long Evans rats were treated by gavage with 0.09, 0.87, or 8.73 mg AMM/kg body weight (BW), vehicle, or 100 mg ATR/kg BW positive control, on gestation days 15-19. Preputial separation was significantly delayed in 0.87 mg and 8.73 mg AMM-exposed males. AMM-exposed males demonstrated a significant treatment-related increase in incidence and severity of inflammation in the prostate on postnatal day (PND) 120. A dose-dependent increase in epididymal fat masses and prostate foci were grossly visible in AMM-exposed offspring. These results indicate that a short, late prenatal exposure to mixture of chlorotriazine metabolites can cause chronic prostatitis in male LE rats. The mode of action for these effects is presently unclear. PMID:20727709

  4. [The effect of the intracerebroventricular administration of vasopressin on the arterial pressure and heart rate of Brattleboro and Long-Evans rats].

    PubMed

    Pencheva, T; Gindeva, R

    1991-01-01

    Vasopressin (VP) was administered in the lateral cerebral ventricles of homozygous rats with congenital diabetes insipidus of Brattleboro (BB) strain as well as of normal animals of Long Evans strain (LE). The following parameters were studied: the latent period for achievement of maximal pressor response in seconds (LP), absolute value of the increase in arterial pressure in comparison with the initial V mmHg (delta AP) and cardiac frequency (CF). The initial values of AP in BB were lower than those values found in LE (BB-9, 10 +/- 0.57 kPa; LE-11, 31 +/- 0.53 kPa; p less than 0.01, while CF showed higher values in BB (350 +/- 8.5 min-1); LE (321 +/- 10 min-1); p less than 0.05. VP, administered intraventricularly, induced quick transitory elevation of AP in both groups, which did not differ substantially both in respect to LP (BB-55 +/- 11 s; LE-43 +/- 6.9) and also in respect to delta AP (BB-3.64 +/- 0.34; LE-3.14 +/- 0.62). CF was not changed in BB (347 +/- 8.9), while it was slightly increased in LE (334 +/- 11). The data show that exogenously administered VP affect the central VP-dependent mechanisms for regulation of AP in the same way in both groups of rats.

  5. Proteomic analysis of the hepatic tissue of Long-Evans Cinnamon (LEC) rats according to the natural course of Wilson disease.

    PubMed

    Lee, Beom H; Kim, Jae-Min; Heo, Sun H; Mun, Joo H; Kim, Jihun; Kim, Joo H; Jin, Hye Y; Kim, Gu-Hwan; Choi, Jin-Ho; Yoo, Han-Wook

    2011-09-01

    Copper-induced toxicity is important in the pathogenic process of Wilson's disease (WD). Using Long-Evans Cinnamon (LEC) rats, an animal model of WD, the study was undertaken to identify proteins involved in the process of WD and to investigate their functional roles in copper-induced hepatotoxicity. In early stages, expression levels of mitochondrial matrix proteins including agmatinase, isovaleryl coenzyme A dehydrogenase, and cytochrome b5 were downregulated. As mitochondrial injuries progressed, along with subsequent apoptotic processes, expressions of malate dehydrogenase 1, annexin A5, transferrin, S-adenosylhomocysteine hydrolase, and sulfite oxidase 1 were differentially regulated. Notably, the expression of malate dehydrogenase 1 was downregulated while the annexin A5 was overexpressed in an age-dependent manner, indicating that these proteins may be involved in the WD process. In addition, pronounced under-expression of S-adenosylhomocysteine hydrolase in elderly LEC rats, also involved in monoamine neurotransmitter metabolism, indicates that this protein might be related to the development of neurological manifestations in WD. The results of our study help to understand the pathogenic process of WD in hepatic tissues, identifying the important proteins associated with the disease process of WD, and to investigate the molecular pathogenic process underlying the development of neurological manifestations in WD.

  6. Pubertal administration of DEHP delays puberty, suppresses testosterone production, and inhibits reproductive tract development in male Sprague-Dawley and Long-Evans rats.

    PubMed

    Noriega, Nigel C; Howdeshell, Kembra L; Furr, Jonathan; Lambright, Christy R; Wilson, Vickie S; Gray, L Earl

    2009-09-01

    Although is clear that exposure to high dosage levels of some phthalates delays the onset of puberty in the male rat, it has been hypothesized that low levels of di(2-ethylhexyl) phthalate (DEHP) accelerate puberty by enhancing testicular androgen synthesis. The current study was designed to determine if the dose response to DEHP was nonmonotonic, as hypothesized. Pubertal administration of DEHP delayed the onset of puberty and reduced androgen-dependent tissue weights in both Long-Evans (LE) and Sprague-Dawley (SD) male rats 300 and 900 mg DEHP/kg/day. These effects were generally of greater magnitude in LE than SD rats. By contrast, alterations in testis histopathology (300 and 900 mg/kg/day) were more severe in SD than in LE rats. Taken together, these results suggest that DEHP may be acting on the pubertal male rat testis via two modes of action; one via the Leydig cells and the other via the Sertoli cells. Treatment with DEHP generally reduced serum testosterone and increased serum luteinizing hormone (LH) levels, demonstrating that the reduction in testosterone was due to the effect of DEHP on the testis and not via an inhibition of LH from hypothalamic-pituitary axis. Testosterone production ex vivo (with and without human chorionic gonadotropin stimulation) was consistently reduced in males at the time of puberty and shortly thereafter. DEHP treatment did not accelerate the age at puberty or enhance testosterone levels at 10 or 100 mg/kg/day in either LE or SD rats, as some have hypothesized. Taken together, these results do not provide any evidence of a nonmonotonic dose response to DEHP during puberty.

  7. The Effect of Atrazine Administered by Gavage or in Diet on the LH Surge and Reproductive Performance in Intact Female Sprague-Dawley and Long Evans Rats

    PubMed Central

    Foradori, Chad D; Sawhney Coder, Prägati; Tisdel, Merrill; Yi, Kun Don; Simpkins, James W; Handa, Robert J; Breckenridge, Charles B

    2014-01-01

    Atrazine (ATR) blunts the hormone-induced luteinizing hormone (LH) surge, when administered by gavage (50–100 mg/kg/day for 4 days), in ovariectomized rats. In this study, we determined if comparable doses delivered either by gavage (bolus dose) or distributed in diet would reduce the LH surge and subsequently affect fertility in the intact female rat. ATR was administered daily to intact female Sprague-Dawley (SD) or Long Evans (LE) rats by gavage (0, 0.75 1.5, 3, 6, 10, 12, 50, or 100 mg/kg/day) or diet (0, 30, 100, 160, 500, 660, or 1460 ppm) during one complete 4-day estrous cycle, starting on day of estrus. Estrous status, corpora lutea, ova, and LH plasma concentrations were evaluated. A second cohort of animals was mated on the fourth treatment day. Fertility metrics were assessed on gestational day 20. A higher portion of LE rats had asynchronous estrous cycles when compared to SD rats both during pretreatment and in response to ATR (≥50 mg/kg). In contrast, bolus doses of ATR (≥50 mg/kg) inhibited the peak and area under the curve for the preovulatory LH surge in SD but not LE animals. Likewise, only bolus-treated SD, not LE, rats displayed reduced mean number of corpora lutea and ova. There were no effects of ATR administered by gavage on mating, gravid number, or fetus number. Dietary administration had no effect on any reproductive parameter measured. These findings indicate that short duration, high-bolus doses of ATR can inhibit the LH surge and reduce the number of follicles ovulated; however, dietary administration has no effect on any endocrine or reproductive outcomes PMID:24831581

  8. The antioxidant effect of DL-alpha-lipoic acid on copper-induced acute hepatitis in Long-Evans Cinnamon (LEC) rats.

    PubMed

    Yamamoto, H; Watanabe, T; Mizuno, H; Endo, K; Fukushige, J; Hosokawa, T; Kazusaka, A; Fujita, S

    2001-01-01

    The Long-Evans Cinnamon (LEC) rats, due to a genetic defect, accumulate excess copper (Cu) in the liver in a manner similar to patients with Wilson's disease and spontaneously develop acute hepatitis with severe jaundice. In this study we examined the protective effect of DL-alpha-Lipoic acid (LA) against acute hepatitis in LEC rats. LA was administered to LEC rats by gavage in doses of 10, 30 and 100 mg/kg five times per week, starting at 8-weeks-old and continuing till 12-weeks-old. Although LA had little effect against the increases in serum transaminase activities, it suppressed the loss of body weight and prevented severe jaundice in a dose-dependent manner. Antioxidant system analyses in liver showed that LA treatment significantly suppressed the inactivations of catalase and glutathione peroxidase, and the induction of heme oxygenase-1, an enzyme which is inducible under oxidative stress. Furthermore, LA showed dose-dependent suppressive effect against increase in nonheme iron contents of both cytosolic and crude mitochondrial fractions in a dose-dependent manner. Although at the highest dose, LA slightly suppressed the accumulation of Cu in crude mitochondrial fraction, it had no effect on the accumulation of Cu in cytosolic fraction. While LA completely suppressed the increase in lipid peroxidation (LPO) in the microsomal fraction at the highest dose, the suppressive effect against LPO in crude mitochondrial fractions was slight. From these results, it is concluded that LA has antioxidant effects at the molecular level against the development of Cu-induced hepatitis in LEC rats. Moreover, mitochondrial oxidative damage might be involved in the development of acute hepatitis in LEC rats.

  9. Dietary polyunsaturated fatty acids suppress acute hepatitis, alter gene expression and prolong survival of female Long-Evans Cinnamon rats, a model of Wilson disease.

    PubMed

    Du, Chunyan; Fujii, Yoichi; Ito, Masafumi; Harada, Manabu; Moriyama, Emiko; Shimada, Ryo; Ikemoto, Atsushi; Okuyama, Harumi

    2004-05-01

    In the Long-Evans Cinnamon rat, copper accumulates in the liver because of a mutation in the copper-transporting ATPase gene, and peroxidative stresses are supposed to be augmented. We examined the effects of dietary fatty acids on hepatitis, hepatic gene expression, and survival. Rats were fed a conventional, low-fat diet (CE2), a CE2 diet supplemented with 10 wt% of lard (Lar), high-linoleic soybean oil (Soy), or a mixture of docosahexaenoic acid (DHA)-rich fish oil and soybean oil (DHA/Soy). Among female rats, the mean survival times of the DHA/Soy and the Soy groups were longer by 17 approximately 20% than in the Lar and the CE2 groups. Among male rats, the survival times were much longer than in the females, but no significant difference in survival was observed among the dietary groups. Serum ceruloplasmin levels in female and male rats of all of the dietary groups were similar. Serum transaminase levels of the DHA/Soy group tended to be lower than in the CE2 group. Histological examinations revealed a marked degeneration in hepatic tissue integrity in the Lar and CE2 groups but not in the DHA/Soy group. Hepatic levels of metal-related genes, transferrin and ceruloplasmin, as well as those related to bile acid synthesis were up-regulated, and an inflammation-related gene (cyclooxygenase [COX]-2) was down-regulated in the DHA/Soy group. Some proliferation-related genes were also affected by the dietary fatty acids. These results indicate that polyunsaturated fatty acids suppress the development of acute hepatitis and prolong survival in females, regardless of whether they are of the n-6 or n-3 type, which are associated with altered gene expressions.

  10. THE TRANSCRIPTIONAL PROFILE OF THE KIDNEY IN TSC2 HETEROZYGOUS MUTANT LONG EVANS (EKER) RATS COMPARED TO WILD-TYPE

    EPA Science Inventory

    Hereditary renal cell carcinoma (RCC) in Eker rats results from an inherited insertional mutation in the Tsc2 tumor suppressor gene and provides a valuable experimental model to characterize the function of the Tsc2 gene product, tuberin in vivo. The Tsc2 mutation predisposes the...

  11. Exposure to methylphenidate during peri-adolescence affects endocrine functioning and sexual behavior in female Long-Evans rats.

    PubMed

    Guarraci, Fay A; Holifield, Caroline; Morales-Valenzuela, Jessica; Greene, Kasera; Brown, Jeanette; Lopez, Rebecca; Crandall, Christina; Gibbs, Nicole; Vela, Rebekah; Delgado, Melissa Y; Frohardt, Russell J

    2016-03-01

    The present study was designed to test the effects of methylphenidate (MPH) exposure on the maturation of endocrine functioning and sexual behavior. Female rat pups received either MPH (2.0mg/kg, i.p.) or saline twice daily between postnatal days 20-35. This period of exposure represents the time just prior to puberty as well as puberty onset. Approximately five weeks after the last injection of MPH or saline, female subjects were hormone-primed and tested during their first sexual experience. Subjects were given the choice to interact with a sexually active male or a sexually receptive female rat (i.e., the partner-preference test). The partner-preference paradigm allows us to assess multiple aspects of female sexual behavior. MPH exposure during peri-adolescence delayed puberty and, when mated for the first time, affected sexual behavior (e.g., increased time spent with the male stimulus and decreased the likelihood of leaving after mounts) during the test of partner preference. When monitoring estrous cyclicity, female subjects treated with MPH during peri-adolescence frequently experienced irregular estrous cycles. The results of the present study suggest that chronic exposure to a therapeutic dose of MPH around the onset of puberty alters long-term endocrine functioning, but with hormone priming, increases sensitivity to sexual stimuli.

  12. Developmental Changes of Catecholamine-mediating Enzyme – Dopamine-β- Hydroxylase and Its Cofactors in Central and Peripheral Tissues and Serum of Long-Evans Rats

    PubMed Central

    Rahman, M. Khalilur; Choudhary, M. Iqbal; Islam, M. Rafiqul; Hafizur, Rahman M.

    2012-01-01

    Dopoamine-β-hydroxylase (DBH) is a catecholamine-synthesizing enzyme which catalyzes the formation of norepinephrine from dopamine. Fifty nine Long-Evans rats of 1 week-old were used to grow on normal diets in 7 different developmental stages, viz., 15 rats in 1 week-old group, 9 rats in 2 weeks-old group, and the remaining 35 rats were divided equally into five groups, 7 rats in each group of 5-, 8-, 12-, 15- and 27-weeks old for systematic developmental studies of DBH. At the end of each developmental period, weights of rats were recorded for that specific group and they were sacrificed. The brain tissues (caudate nucleus, hypothalamus, brain stem, colliculi, cerebral cortex and cerebellum) and peripheral tissues (liver, heart, kidney, adrenal, spleen, pancreas, lung and small intestine) and serum were collected. The brain tissues had the highest activity (expressed as nmole/min/g of wet weight tissue) of DBH at 5 weeks of age. The hypothalamus had the highest activities (11.5 ± 2.2) and the lowest activities were found in the cerebellum (5.7 ± 0.9). The peripheral tissues also showed the peak DBH activities at 5 weeks of age and adrenals had the highest activities (59.2 ± 7.0) among the central and peripheral tissues. The serum DBH activities were relatively low (1.3 ± 0.2) as compared to those in all other tissues. The highest serum DBH activities (1.28 ± 21 nmole/min/ml of serum) were also found in the 5- weeks-old rats. The specific activities of DBH were also measured in various developmental stages and the results were found to be in agreement with the DBH activities expressed in terms of gram of tissues or milliliter of serum. The Km and Vmax values for DBH were measured in the serum samples of each group and the highest Vmax values (78.3 ± 21.2 pmol/min/mg protein) were obtained at 5 weeks of age; while the lowest Km values (0.52 ± 0.04 mM) were obtained at this stage of age. PMID:23675273

  13. Paper or Plastic? Exploring the Effects of Natural Enrichment on Behavioural and Neuroendocrine Responses in Long-Evans Rats.

    PubMed

    Bardi, M; Kaufman, C; Franssen, C; Hyer, M M; Rzucidlo, A; Brown, M; Tschirhart, M; Lambert, K G

    2016-05-01

    Enriched environments are beneficial to neurobiological development; specifically, rodents exposed to complex, rather than standard laboratory, environments exhibit evidence of neuroplasticity and enhanced cognitive performance. In the present study, the nature of elements placed in the complex environment was investigated. Accordingly, rats (n = 8 per group) were housed either in a natural environment characterised by stimuli such as dirt and rocks, an artificial environment characterised by plastic toys and synthetic nesting materials, a natural/artificial environment characterised by a combination of artificial and natural stimuli or a laboratory standard environment characterised by no enrichment stimuli. Following exposure to emotional and cognitive behavioural tasks, including a cricket hunting task, a novel object preference task and a forced swim task, brains were processed for glial fibrillary acidic protein (GFAP)-, neuronal nuclei (NeuN)- and brain-derived neurotrophic factor (BDNF) immunoreactivity. Baseline and stress foecal samples were collected to assess corticosterone (CORT) and dehydroepiandrosterone (DHEA). Natural environment animals exhibited shorter diving latencies and increased diving frequencies in the second forced swimming task, along with higher DHEA/CORT ratios, and higher GFAP immunoreactivity in the hippocampus. The type of environmental enrichment did not influence levels of BDNF immunoreactivity in the CA1, CA3 and dentate gyrus of the hippocampus; however, natural environment animals exhibited higher levels of NeuN immunoreactivity in the retrosplenial cortex, an area involved in spatial memory and other cognitive functions. These results suggest that, in addition to enhancing behavioural and endocrinological variables associated with resilience, exposure to natural stimuli might alter plasticity in brain areas associated with cortical processing and learning.

  14. Paper or Plastic? Exploring the Effects of Natural Enrichment on Behavioural and Neuroendocrine Responses in Long-Evans Rats.

    PubMed

    Bardi, M; Kaufman, C; Franssen, C; Hyer, M M; Rzucidlo, A; Brown, M; Tschirhart, M; Lambert, K G

    2016-05-01

    Enriched environments are beneficial to neurobiological development; specifically, rodents exposed to complex, rather than standard laboratory, environments exhibit evidence of neuroplasticity and enhanced cognitive performance. In the present study, the nature of elements placed in the complex environment was investigated. Accordingly, rats (n = 8 per group) were housed either in a natural environment characterised by stimuli such as dirt and rocks, an artificial environment characterised by plastic toys and synthetic nesting materials, a natural/artificial environment characterised by a combination of artificial and natural stimuli or a laboratory standard environment characterised by no enrichment stimuli. Following exposure to emotional and cognitive behavioural tasks, including a cricket hunting task, a novel object preference task and a forced swim task, brains were processed for glial fibrillary acidic protein (GFAP)-, neuronal nuclei (NeuN)- and brain-derived neurotrophic factor (BDNF) immunoreactivity. Baseline and stress foecal samples were collected to assess corticosterone (CORT) and dehydroepiandrosterone (DHEA). Natural environment animals exhibited shorter diving latencies and increased diving frequencies in the second forced swimming task, along with higher DHEA/CORT ratios, and higher GFAP immunoreactivity in the hippocampus. The type of environmental enrichment did not influence levels of BDNF immunoreactivity in the CA1, CA3 and dentate gyrus of the hippocampus; however, natural environment animals exhibited higher levels of NeuN immunoreactivity in the retrosplenial cortex, an area involved in spatial memory and other cognitive functions. These results suggest that, in addition to enhancing behavioural and endocrinological variables associated with resilience, exposure to natural stimuli might alter plasticity in brain areas associated with cortical processing and learning. PMID:26970429

  15. Inactivating the infralimbic but not prelimbic medial prefrontal cortex facilitates the extinction of appetitive Pavlovian conditioning in Long-Evans rats.

    PubMed

    Mendoza, J; Sanio, C; Chaudhri, N

    2015-02-01

    The infralimbic medial prefrontal cortex (IL) has been posited as a common node in distinct neural circuits that mediate the extinction of appetitive and aversive conditioning. However, appetitive extinction is typically assessed using instrumental conditioning procedures, whereas the extinction of aversive conditioning is customarily studied using Pavlovian assays. The role of the IL in the extinction of appetitive Pavlovian conditioning remains underexplored. We investigated the involvement of the IL and prelimbic medial prefrontal cortex (PrL) in appetitive extinction in Pavlovian and instrumental conditioning assays in male, Long-Evans rats. Following acquisition, a gamma-aminobutyric acid agonist solution (0.03 nmol muscimol; 0.3 nmol baclofen; 0.3 μl/side) was bilaterally microinfused into the IL or PrL to pharmacologically inactivate each region before the first extinction session. Compared to saline, PrL inactivation did not affect the acquisition of extinction or the recall of extinction memory 24-h later. IL inactivation caused a more rapid extinction of Pavlovian conditioning, but had no effect on the extinction of instrumental conditioning or extinction recall. IL inactivation during a Pavlovian conditioning session in which conditioned stimulus (CS) trials were paired with sucrose did not affect CS-elicited behaviour, but increased responding during intervals that did not contain the CS. The same manipulation did not impact lever pressing for sucrose. These findings suggest that the IL may normally maintain Pavlovian conditioned responding when an anticipated appetitive CS is unexpectedly withheld, and that this region has distinct roles in the expression of Pavlovian conditioning when an appetitive unconditioned stimulus is either presented or omitted.

  16. Increased expression of hepatic pyruvate dehydrogenase kinases 2 and 4 in young and middle-aged Otsuka Long-Evans Tokushima Fatty rats: induction by elevated levels of free fatty acids.

    PubMed

    Bajotto, Gustavo; Murakami, Taro; Nagasaki, Masaru; Qin, Bolin; Matsuo, Yoshiyuki; Maeda, Ken; Ohashi, Masayo; Oshida, Yoshiharu; Sato, Yuzo; Shimomura, Yoshiharu

    2006-03-01

    The activity of the pyruvate dehydrogenase complex (PDC) is regulated by covalent modification of its E1 component, which is catalyzed by specific pyruvate dehydrogenase kinases (PDKs) and phosphatases. In the liver, PDK2 and PDK4 are the most abundant PDK isoforms, which are responsible for inactivation of PDC when glucose availability is scarce in the body. In the present study, regulatory mechanisms of hepatic PDC were examined before and after the onset of type 2 diabetes mellitus in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, using Long-Evans Tokushima Otsuka (LETO) rats as controls. Plasma glucose and insulin concentrations were at normal levels in rats aged 8 weeks, but were significantly higher in OLETF than in LETO rats aged 25 weeks, indicating insulin resistance in OLETF rats. Plasma free fatty acids (FFAs) were 1.6-fold concentrated, and the liver PDC activity was significantly lower in OLETF than in LETO rats at both ages, suggesting suppression of pyruvate oxidative decarboxylation in OLETF rats before and after the onset of diabetes. Pyruvate dehydrogenase kinase activity and abundance of PDK2 and PDK4 proteins, as well as mRNAs, were greater in OLETF rats at both ages. These results suggest that persistently elevated levels of circulating free fatty acid in normal and diabetic OLETF rats play an important role in stimulating PDK2 and PDK4 expression in liver. PMID:16483874

  17. Thermoregulatory deficits in adult long evans rat offspring exposed perinatally to the antithyroidal drug, propylthiouracil

    EPA Science Inventory

    Developmental exposure to endocrine disrupting toxicants has been shown to alter a variety of physiological processes in mature offspring. Body (core) temperature (Tc) is a tightly regulated homeostatic system but is susceptible to disruptors of the hypothalamic-pituitary-thyroid...

  18. Investigation of Metabolism of Exogenous Glucose at the Early Stage and Onset of Diabetes Mellitus in Otsuka Long-Evans Tokushima Fatty Rats Using [1, 2, 3-13C]Glucose Breath Tests

    PubMed Central

    Kijima, Sho; Tanaka, Hideki

    2016-01-01

    This study aimed to evaluate changes in glucose metabolism at the early stage and onset of diabetes in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Specifically, after the oral administration of [1, 2, 3-13C]glucose, the levels of exhaled 13CO2, which most likely originated from pyruvate decarboxylation and tricarboxylic acid, were measured. Eight OLETF rats and eight control rats (Long-Evans Tokushima Otsuka [LETO]) were administered 13C-glucose. Three types of 13C-glucose breath tests were performed thrice in each period at 2-week intervals. [3-13C]glucose results in a 13C isotope at position 1 in the pyruvate molecule, which provides 13CO2. The 13C at carbons 1 and 2 of glucose is converted to 13C at carbons 2 and 1 of acetate, respectively, which produce 13CO2. Based on metabolic differences of the labeled sites, glucose metabolism was evaluated using the results of three breath tests. The increase in 13CO2 excretion in OLETF rats was delayed in all three breath tests compared to that in control rats, suggesting that OLETF rats had a lower glucose metabolism than control rats. In addition, overall glucose metabolism increased with age in both groups. The utilization of [2-13C]glucose was suppressed in OLETF rats at 6–12 weeks of age, but they showed higher [3-13C]glucose oxidation than control rats at 22–25 weeks of age. In the [1-13C]glucose breath test, no significant differences in the area under the curve until 180 minutes (AUC180) were observed between OLETF and LETO rats of any age. Glucose metabolism kinetics were different between the age groups and two groups of rats; however, these differences were not significant based on the overall AUC180 of [1-13C]glucose. We conclude that breath 13CO2 excretion is reduced in OLETF rats at the primary stage of prediabetes, indicating differences in glucose oxidation kinetics between OLETF and LETO rats. PMID:27483133

  19. Comparison of spatial learning in the partially baited radial-arm maze task between commonly used rat strains: Wistar, Spargue-Dawley, Long-Evans, and outcrossed Wistar/Sprague-Dawley.

    PubMed

    Gökçek-Saraç, Çiğdem; Wesierska, Malgorzata; Jakubowska-Doğru, Ewa

    2015-03-01

    Strain-related differences in animals' cognitive ability affect the outcomes of experiments and may be responsible for discrepant results obtained by different research groups. Therefore, behavioral phenotyping of laboratory animals belonging to different strains is important. The aim of the present study was to compare the variation in allothetic visuospatial learning in most commonly used laboratory rat strains: inbred Wistar (W) and Sprague-Dawley (SD), outcrossed Wistar/Sprague-Dawley (W/SD), and outbred Long Evans (LE) rats. All rats were trained to the arbitrary performance criterion of 83 % correct responses in the partially baited 12-arm radial maze allowing for simultaneous evaluation of both working and reference memory. In the present study, testing albino versus pigmented and inbred versus outcrossed rats revealed significant strain-dependent differences with the inbred SD rats manifesting lower performance on all learning measures compared to other strains. On the other hand, the outcrossed W/SD rats showed a lower frequency of reference memory errors and faster rate of task acquisition compared to both LE and W rats, with W rats showing a lower frequency of working memory errors compared to other strains. In conclusion, albinism apparently did not reduce the animals' performance in the allothetic visuospatial learning task, while outcrossing improved the spatial learning. A differential effect of strain on the contribution of each error type to the animals' overall performance was observed. The strain-dependent differences were more pronounced between subpopulations of learning-deficient individuals ("poor" learners), and generally the reference memory errors contributed more to the final behavioral output than did the working memory errors. PMID:25537841

  20. Effects of Prenatal Exposure to a Low Dose Atrazine Metabolite Mixture on pubertal timing and prostrate Development of Male Long Evans Rats.

    EPA Science Inventory

    The present study examines the postnatal reproductive development of male rats following prenatal exposure to an atrazine metabolite mixture (AMM) consisting of the herbicide atrazine and its environmental metabolites diaminochlorotriazine, hydroxyatrazine, deethylatrazine, and d...

  1. Analysis of preneoplastic and neoplastic renal lesions in Tsc2 mutant Long-Evans (Eker) rats following exposure to a mixture of drinking water disinfection by-products.

    PubMed

    McDorman, Kevin S; Hooth, Michelle J; Starr, Thomas B; Wolf, Douglas C

    2003-05-01

    Disinfection of surface water for human consumption results in the generation of a complex mixture of chemicals in potable water. Cancer risk assessment methodology assumes additivity of carcinogenic effects in the regulation of mixtures. A rodent model of hereditary renal cancer was used to investigate the carcinogenic response to a mixture of drinking water disinfection by-products (DBPs). Rats carrying a mutation in the Tsc2 tumor suppressor gene (Eker rats) readily develop renal preneoplastic and neoplastic lesions, and are highly susceptible to the effects of renal carcinogens. Male and female Eker rats were exposed via drinking water to individual or a mixture of DBPs for 4 or 10 months. Potassium bromate, 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), chloroform, and bromodichloromethane were administered at low concentrations of 0.02, 0.005, 0.4 and 0.07 g/l, respectively, and high concentrations of 0.4, 0.07, 1.8 and 0.7 g/l, respectively. Low and high dose mixture solutions were comprised of all four chemicals at either low concentrations or high concentrations, respectively, Following necropsy, each kidney was examined microscopically for preneoplastic lesions (atypical tubules and hyperplasias) and tumors. While some of the mixture responses observed in male rats did fall within the range expected for an additive response, especially at the high dose, predominantly antagonistic effects on renal lesions were observed in response to the low dose mixture in male rats and the high dose mixture in female rats. These data suggest that current default risk assessments assuming additivity may overstate the cancer risk associated with exposure to mixtures of DBPs at low concentrations. PMID:12679048

  2. Long-term treatment of aged Long Evans rats with a dietary supplement containing neuroprotective peptides (N-PEP-12) to prevent brain aging: effects of three months daily treatment by oral gavage.

    PubMed

    Hutter-Paier, B; Reininger-Gutmann, B; Wronski, R; Doppler, E; Moessler, H

    2015-01-01

    Aging is associated with morphological and functional changes in the brain, resulting in the deterioration of cognitive performance. Growth factors like BDNF are suggested to be involved in the regulation of age-related processes in the brain. A novel dietary supplement produced from purified nerve cell proteins, N-PEP-12, has shown to share properties with naturally occurring peptide growth factors by stimulating neurite outgrowth and beneficial effects on neuronal survival and protection against metabolic stress in cell cultures. The current study investigates the effects of long-term intake on age-dependent memory decline by assessing cognitive performance and synaptic density. All the experiments were performed in aged Long Evans rats randomly assigned to saline or N-PEP-12 once daily by gavage over a period of three months. Behavioral tests were performed in the Morris Water Maze after one, two and three months of treatment. Histological examinations were performed in the hippocampal formation and in the entorhinal cortex by measuring the synaptic density. This study shows that the oral intake of N-PEP-12 has beneficial effects on the cognitive performance of aged animals and that these effects go along with an increase in the synaptic density. Thus, N-PEP-12 may help maintain memory and learning performance during the aging process.

  3. Pubertal administration of DEHP delays puberty, suppresses testosterone production and inhibits reproductive tract development in male Sprague-Dawley and Long-Evans Rats

    EPA Science Inventory

    While is clear that exposure to high dosage levels of some phthalates delays the onset of puberty in the male rat it has been hypothesized that low levels of DEHP accelerate puberty by enhancing testicular androgen synthesis. The current study was designed to determine if the do...

  4. Patterns of Toxoplasma gondii cyst distribution in the forebrain associate with individual variation in predator odor avoidance and anxiety-related behavior in male Long-Evans rats

    PubMed Central

    Evans, Andrew K.; Strassmann, Patrick S.; Lee, I-Ping; Sapolsky, Robert M.

    2014-01-01

    Toxoplasma gondii (T. gondii) is one of the world’s most successful brain parasites. T. gondii engages in parasite manipulation of host behavior and infection has been epidemiologically linked to numerous psychiatric disorders. Mechanisms by which T. gondii alters host behavior are not well understood, but neuroanatomical cyst presence and the localized host immune response to cysts are potential candidates. The aim of these studies was to test the hypothesis that T. gondii manipulation of specific host behaviors is dependent on neuroanatomical location of cysts in a time-dependent function post-infection. We examined neuroanatomical cyst distribution (53 forebrain regions) in infected rats after predator odor aversion behavior and anxiety-related behavior in the elevated plus maze and open field arena, across a 6-week time course. In addition, we examined evidence for microglial response to the parasite across the time course. Our findings demonstrate that while cysts are randomly distributed throughout the forebrain, individual variation in cyst localization, beginning 3 weeks post-infection, can explain individual variation in the effects of T. gondii on behavior. Additionally, not all infected rats develop cysts in the forebrain, and attenuation of predator odor aversion and changes in anxiety-related behavior are linked with cyst presence in specific forebrain areas. Finally, the immune response to cysts is striking. These data provide the foundation for testing hypotheses about proximate mechanisms by which T. gondii alters behavior in specific brain regions, including consequences of establishment of a homeostasis between T. gondii and the host immune response. PMID:24269877

  5. TIME COURSE OF CHOLINESTERASE INHIBITION IN ADULT RATS TREATED ACUTELY WITH CARBARYL CARBOFURAN, FORMETANATE, METHOMYL, METHIOCARB, OXAMYL ON PROPOXUR.

    EPA Science Inventory

    To compare the toxicity of seven N-methyl carbamates, time course profiles for brain and red blood cell (RBC) cholinesterase (ChE) inhibition were established for each. Adult, male, Long Evans rats (n=4-5 dose group) were dosed orally with either carbaryl (30 mg/kg in corn oil); ...

  6. TIME COURSE AND DOSE RESPONSE ASSESSMENT OF CHOLINESTERASE (CHE) INHIBITION IN ADULT RATS TREATED ACUTELY WITH CARBARYL, METHOMYL, METHIOCARB, OXAMYL, OR PROPOXUR.

    EPA Science Inventory

    To compare the toxicity of 5 N-methyl carbamates, the time course and dose response profiles for ChE inhibition were established for each. For the time course comparison, adult male Long Evans rats (n=5 dose group) were dosed orally with either carbaryl (CB; 30 mg/kg in corn oi...

  7. A DOSE–RESPONSE ANALYSIS OF THE REPRODUCTIVE EFFECTS OF A SINGLE GESTATIONAL DOSE OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN IN MALE LONG EVANS HOODED RAT OFFSPRING

    EPA Science Inventory

    Male rats exposed in utero to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) display reduced fertility as a consequence of the direct action of TCDD on the epididymides, as well as delayed puberty and altered reproductive organ weights. The current study provides dose-response data f...

  8. Effects of Fipronil on the EEG of Long Evans Rats

    EPA Science Inventory

    We have reported that the non-stimulus driven EEG is differentially altered by deltamethrin or permethrin (Lyke and Herr, Toxicologist, 114(S-1):265, 2010). In the current study, we examined the ability to detect changes in EEG activity produced by fipronil, a phenylpyrazole pest...

  9. Estrogen effects on the forced swim test differ in two outbred rat strains

    PubMed Central

    Koss, Wendy A.; Einat, Haim; Schloesser, Robert J.; Manji, Husseini K.; Rubinow, David R.

    2012-01-01

    Changes in reproductive hormones, such as estrogen, play a role in mood regulation. The present study examined strain differences (Long-Evans vs. Wistar-Hannover) in the behavioral and biochemical effects of estrogen manipulation. Adult ovariectomized female rats were treated with estradiol, vehicle, or withdrawn from estradiol. The two strains demonstrated differential behavioral responses to short-term estradiol administration in the forced swim test; estradiol induced an antidepressant-like effect in Long-Evans rats but not in Wistar rats. Conversely, withdrawal from estradiol resulted in a depressive-like state in the Wistar rats but not in the Long-Evans rats. Western blot analyses found no differences in estrogen receptors α and β within the hippocampus or the frontal cortex, two brain areas strongly implicated in affective disorders. These data demonstrate the importance of strain as a variable when interpreting behavioral effects of estrogen. PMID:22266677

  10. In vitro dermal absorption of pyrethroid pesticides in human and rat skin

    EPA Science Inventory

    Dermal exposure to pyrethroid pesticides can occur during manufacture and application. This study examined the in vitro dermal absorption of pyrethroids using rat and human skin. Dermatomed skin from adult male Long Evans rats or human cadavers was mounted in flowthrough diffusi...

  11. TOLERANCE AND SENSITIZATION TO WEEKLY NICOTINE EXPOSURES ON THE MOTOR ACTIVITY OF RATS.

    EPA Science Inventory

    Motor activity was examined in adult female Long-Evans rats in a photocell device during daily (M-F) 30-min sessions. Following adaptation to the testing routine the rats were divided into six groups of eight that were designated to receive either nothing (non-injected control),...

  12. CHLORPYRIFOS AND 3,5,6 TRICHLORO-2-PYRIDINOL DISTRIBUTION IN RAT BLOOD AND BRAIN DURING CHRONIC DIETARY AND REPEATED HIGH LEVEL ACUTE EXPOSURE TO CHLORPYRIFOS.

    EPA Science Inventory

    The aim of this study was to determine the concentrations of an organophosphorus pesticide, chlorpyrifos (CPF), and the metabolite 3,5,6 trichloro-2-pyridinol (TCP) in tissues from rats exposed to long-term, low-dose CPF. Adult, Long-Evans male rats received CPF for one year at ...

  13. Response Acquisition and Fixed-Ratio Escalation Based on Interresponse Times in Rats

    ERIC Educational Resources Information Center

    Taylor, Tracy G.; Galuska, Chad M.; Banna, Kelly; Yahyavi-Firouz-Abadi, Noushin; See, Ronald E.

    2010-01-01

    The effectiveness of a fixed-ratio (FR) escalation procedure, developed by Pinkston and Branch (2004) and based on interresponse times (IRTs), was assessed during lever-press acquisition. Forty-nine experimentally naive adult male Long Evans rats were deprived of food for 24 hr prior to an extended acquisition session. Before the start of the…

  14. NEUROBEHAVIORAL EFFECTS OF CHRONIC DIETARY AND REPEATED HIGH-LEVEL SPIKE EXPOSURE TO CHLORPYRIFOS IN RATS.

    EPA Science Inventory

    This study aimed to model long-term subtoxic human exposure to an organophosphorus pesticide, chlorpyrifos, and to examine the influence of that exposure on the response to intermittent high-dose acute challenges. Adult Long-Evans male rats were maintained at 350g body weight by...

  15. NEUROBEHAVIORAL EVALUATION OF RATS EXPOSED TO CHLORPYRIFOS VIA CHRONIC DIETARY AND REPEATED HIGH-LEVEL SPIKE EXPOSURE.

    EPA Science Inventory

    This study aimed to model long-term subtoxic human exposure to an organophosphorus pesticide, chlorpyrifos (CPF), and to examine the influence of that exposure on the response to intermittent high-dose acute challenges. Adult Long-Evans male rats were maintained at 350g body wei...

  16. Adult Rats Treated with Risperidone during Development Are Hyperactive

    PubMed Central

    Bardgett, Mark E.; Franks-Henry, Julie M.; Colemire, Kristin R.; Juneau, Kathleen R.; Stevens, Rachel M.; Marczinski, Cecile A.; Griffith, Molly S.

    2014-01-01

    Risperidone is an antipsychotic drug approved for use in children, but little is known about the long-term effects of early-life risperidone treatment. In animals, prolonged risperidone administration during development increases forebrain dopamine receptor expression immediately upon the cessation of treatment. A series of experiments was performed to ascertain whether early-life risperidone administration altered locomotor activity, a behavior sensitive to dopamine receptor function, in adult rats. One additional behavior modulated by forebrain dopamine function, spatial reversal learning, was also measured during adulthood. In each study, Long-Evans rats received daily subcutaneous injections of vehicle or one of two doses of risperidone (1.0 and 3.0 mg/kg per day) from postnatal days 14 – 42. Weight gain during development was slightly yet significantly reduced in risperidone-treated rats. In the first two experiments, early-life risperidone administration was associated with increased locomotor activity at one week post-administration through approximately nine months of age, independent of changes in weight gain. In a separate experiment, it was found that the enhancing effect of early-life risperidone on locomotor activity occurred in males and female rats. A final experiment indicated that spatial reversal learning was unaffected in adult rats administered risperidone early in life. These results indicate that locomotor activity during adulthood is permanently modified by early-life risperidone treatment. The findings suggest that chronic antipsychotic drug use in pediatric populations (e.g., treatment for the symptoms of autism) could modify brain development and alter neural set-points for specific behaviors during adulthood. PMID:23750695

  17. CYP 450 enzyme induction by chronic oral musk xylene in adult and developing rats.

    PubMed

    Suter-Eichenberger, R; Boelsterli, U A; Conscience-Egli, M; Lichtensteiger, W; Schlumpf, M

    2000-04-10

    Developmental and adult toxicity of musk xylene was studied in Long Evans (LE) rats fed with chow containing musk xylene (MX) in food pellets in concentrations of 1 mg, 10 mg, 33 mg, 100 mg and 1000 mg MX per 1 kg chow corresponding to a daily intake of 0.07-0.08 mg MX/kg up to 70-80 mg MX/kg body weight. Adult male and female rats were MX exposed for a minimum of 10 weeks before mating. Exposure continued throughout pregnancy, birth and lactation. The effects of MX on CYP1A1/1A2 were studied in liver microsomes by EROD (7-ethoxyresorufin-rosomes deethylase) for CYP1A1 and by MROD (methoxyresorufin-o-demethylase) for CYP1A2 activity and by Western blotting. MX induced these enzymes dose dependently in adult and developing rats at PN (postnatal day) 1 and 14. The lowest effective maternal dose was 2-3 mg MX/kg/day. Western blot data of CYP2B and CYP3A indicated the induction of both P450 enzyme proteins in developing rats at PN 14 at the higher dose of 70-80 mg MX/kg/day. In contrast, upon high MX exposure CYP2B but not CYP3A was found to be induced in adult first generation male and female rats, indicating differential sensitivity to MX in development.

  18. CYP 450 enzyme induction by chronic oral musk xylene in adult and developing rats.

    PubMed

    Suter-Eichenberger, R; Boelsterli, U A; Conscience-Egli, M; Lichtensteiger, W; Schlumpf, M

    1999-12-20

    Developmental and adult toxicity of musk xylene was studied in Long Evans (LE) rats fed with chow containing musk xylene (MX) in food pellets in concentrations of 1 mg, 10 mg, 33 mg, 100 mg and 1000 mg MX per 1 kg chow corresponding to a daily intake of 0.07-0.08 mg MX/kg up to 70-80 mg MX/kg body weight. Adult male and female rats were MX exposed for a minimum of 10 weeks before mating. Exposure continued throughout pregnancy, birth and lactation. The effects of MX on CYP1A1/1A2 were studied in liver microsomes by EROD (7-ethoxyresorufin-o-deethylase) for CYP1A1 and by MROD (methoxyresorufin-o-demethylase) for CYP1A2 activity and by Western blotting. MX induced these enzymes dose dependently in adult and developing rats at PN (postnatal day) 1 and 14. The lowest effective maternal dose was 2-3 mg MX/kg/day. Western blot data of CYP2B and CYP3A indicated the induction of both P450 enzyme proteins in developing rats at PN 14 at the higher dose of 70-80 mg MX/kg/day. In contrast, upon high MX exposure CYP2B but not CYP3A was found to be induced in adult first generation male and female rats, indicating differential sensitivity to MX in development.

  19. ATRAZINE INCREASES DIMETHYLBENZ[A]ANTHRACENE-INDUCED MAMMARY TUMOR INCIDENCE IN LONG EVANS OFFSPRING EXPOSED IN UTERO

    EPA Science Inventory

    ATRAZINE INCREASES DIMETHYLBENZ[A]ANTHRACENE-INDUCED MAMMARY TUMOR INCIDENCE IN LONG EVANS OFFSPRING EXPOSED IN UTERO.

    SE Fenton and CC Davis

    Reproductive Toxicology Division, NHEERL, ORD, USEPA, Durham, NC, USA

    Recently, we found that ATR exposure during ma...

  20. Spaced training facilitates long-term retention of place navigation in adult but not in adolescent rats.

    PubMed

    Spreng, Matthieu; Rossier, Jérôme; Schenk, Françoise

    2002-01-01

    Young and adult Long Evans rats were tested in the water maze according to two different procedures: half of the subjects were given one session of four trials a day for 6 days, whereas the other subjects had the same amount of training massed in 1 day. For both conditions, a 14-day retention interval was then introduced to test long-term memory. This was followed by a four-trial reversal session. All groups showed a significant learning curve, but escape latencies were shorter for the adult than for the young rats, without differential effect of the training procedure. A first probe trial (PT1) confirmed similar accurate short-term retention in all the groups. But unimpaired long-term memory was only seen in the adult rats trained with the spaced procedure. The young rats trained over 1 day also showed some retention of the platform location after 14 days, but not the other two groups. Reversal acquisition of the new platform location was rapid in the four groups. These results indicate that although accurate short-term spatial memory in the water maze is seen after a 1-day massed training in both age groups, unimpaired long-term retention is only observed in adult rats trained with 24-h inter-session intervals.

  1. Differential effects of neonatal handling on anxiety, corticosterone response to stress, and hippocampal glucocorticoid and serotonin (5-HT)2A receptors in Lewis rats.

    PubMed

    Durand, M; Sarrieau, A; Aguerre, S; Mormède, P; Chaouloff, F

    1998-05-01

    Neonatal handling (during the first 3 weeks of age) has been reported by others to diminish the hypothalamo-pituitary-adrenal (HPA) responsivity to stress in adult Long Evans rats, an effect involving a serotonin (5-HT)2A receptor-mediated increase in glucocorticoid receptor (GR) gene expression in the frontal cortex and the hippocampus. In addition, handled animals may also display enduring reductions in anxiety-related behaviours, including in the elevated plus-maze. We have thus analysed the aforementioned neuroendocrine and behavioural consequences of neonatal stress in male and female adult Lewis rats, a strain characterised by its high anxiety and its hyporesponsive HPA axis. Plasma corticosterone, but not behavioural, responses to an elevated plus-maze test were decreased in handled rats. Besides, hippocampal mineralocorticoid receptor (MR) and GR binding capacities were not different between handled and non-handled Lewis rats, an observation which could be extended to our adult Long Evans rats. Lastly, neither hippocampal nor cortical 5-HT2A receptor binding capacities in adult Lewis rats were affected by prior handling. In keeping with the failure to detect early handling-induced increases in hippocampal GR binding in 3-week old Lewis and Long Evans rats, the present study reinforces past findings indicating that environmental and genetic factors are crucial variables in the neonatal handling paradigm.

  2. Astrocytes in the Rat Medial Amygdala Are Responsive to Adult Androgens

    PubMed Central

    Johnson, Ryan T.; Schneider, Amanda; DonCarlos, Lydia L.; Breedlove, S. Marc; Jordan, Cynthia L.

    2014-01-01

    The posterodorsal medial amygdala (MePD) exhibits numerous sex differences including differences in volume and in the number and morphology of neurons and astroctyes. In adulthood, gonadal hormones, including both androgens and estrogens, have been shown to play a role in maintaining the masculine character of many of these sex differences, but whether adult gonadal hormones maintain the increased number and complexity of astrocytes in the male MePD was unknown. To answer this question we examined astrocytes in the MePD of male and female Long Evans rats that were gonadectomized as adults and treated for 30 days with either testosterone or a control treatment. At the end of treatment brains were collected and immunostained for glial fibrillary acidic protein. Stereological analysis revealed that adult androgen levels influenced the number and complexity of astrocytes in the MePD of both sexes, but the specific effects of androgens were different in males and females. However, sex differences in the number and complexity of adult astrocytes persisted even in the absence of gonadal hormones in adulthood, suggesting that androgens also act earlier in life to determine these adult sex differences. Using immunofluorescence and confocal microscopy, we found robust androgen receptor immunostaining in a subpopulation of MePD astrocytes, suggesting that testosterone may act directly on MePD astrocytes to influence their structure and function. PMID:22581688

  3. Desvenlafaxine may accelerate neuronal maturation in the dentate gyri of adult male rats.

    PubMed

    Asokan, Aditya; Ball, Alan R; Laird, Christina D; Hermer, Linda; Ormerod, Brandi K

    2014-01-01

    Adult hippocampal neurogenesis has been linked to the effects of anti-depressant drugs on behavior in rodent models of depression. To explore this link further, we tested whether the serotonin-norepinephrine reuptake inhibitor (SNRI) venlafaxine impacted adult hippocampal neurogenesis differently than its primary active SNRI metabolite desvenlafaxine. Adult male Long Evans rats (n = 5-6 per group) were fed vehicle, venlafaxine (0.5 or 5 mg) or desvenlafaxine (0.5 or 5 mg) twice daily for 16 days. Beginning the third day of drug treatment, the rats were given a daily bromodeoxyuridine (BrdU; 50 mg/kg) injection for 5 days to label dividing cells and then perfused 2 weeks after the first BrdU injection to confirm total new hippocampal cell numbers and their phenotypes. The high desvenlafaxine dose increased total new BrdU+ cell number and appeared to accelerate neuronal maturation because fewer BrdU+ cells expressed maturing neuronal phenotypes and more expressed mature neuronal phenotypes in the dentate gyri of these versus vehicle-treated rats. While net neurogenesis was not increased in the dentate gyri of rats treated with the high desvenlafaxine dose, significantly more mature neurons were detected. Our data expand the body of literature showing that antidepressants impact adult neurogenesis by stimulating NPC proliferation and perhaps the survival of neuronal progeny and by showing that a high dose of the SNRI antidepressant desvenlafaxine, but neither a high nor low venlafaxine dose, may also accelerate neuronal maturation in the adult rat hippocampus. These data support the hypothesis that hippocampal neurogenesis may indeed serve as a biomarker of depression and the effects of antidepressant treatment, and may be informative for developing novel fast-acting antidepressant strategies.

  4. BEHAVIORAL ASSESSMENTS OF LONG EVANS RATS FOLLOWING A 13-WEEK SUBCHRONIC TOLUENE EXPOSURE.

    EPA Science Inventory

    The current study sought to develop an animal model of the neurotoxicity of long-term exposure to volatile organic compounds (VOCs) which may be used to predict the effects of chronic exposure to VOCs on public health. The effects of Subchronic inhalation exposure to toluene (0,...

  5. Toluene Inhalation Exposure for 13 Weeks Causes Persistent Changes in Electroretinograms of Long-Evans Rats

    EPA Science Inventory

    Studies of humans chronically exposed to volatile organic solvents have reported impaired visual functions, including low contrast sensitivity and reduced color discrimination. These reports, however, lacked confirmation from controlled laboratory experiments. To addre...

  6. THE DEVELOPMENTAL TOXICITY OF BROMOCHLOROACETONITRILE IN PREGNANT LONG-EVANS RATS

    EPA Science Inventory

    Bromochloroacetonitrile (BCAN) is a by-product of the chlorine disinfection of water containing natural organic material. Adverse effects of BCAN in an in vivo teratology screen (i.e. neonatal survival assay) gave reason for further investigation into the developmental toxicity o...

  7. VISUAL FUNCTION CHANGES AFTER SUBCHRONIC TOLUENE INHALATION IN LONG-EVANS RATS.

    EPA Science Inventory

    Chronic exposure to volatile organic compounds, including toluene, has been associated with visual deficits such as reduced visual contrast sensitivity or impaired color discrimination in studies of occupational or residential exposure. These reports remain controversial, howeve...

  8. IMIDACLOPRID PRODUCES MINIMAL CHANGES IN THE EEG OF LONG-EVANS RATS

    EPA Science Inventory

    We have reported that the non-stimulus driven EEG is differentially altered by deltamethrin or permethrin (Lyke and Herr, Toxicologist, 114(S-1) :265, 2010) as well as fipronil (Lyke and Herr, Toxicologist, 120(S-2) :290, 2011). In the current study, we examined the ability to de...

  9. Acute triadimefon-induced changes in the EEG of Long-Evans Rats

    EPA Science Inventory

    We have reported that the non-stimulus driven EEG is altered differently by acute treatment with deltamethrin, permethrin, fipronil, or imidacloprid (Lyke and Herr, Lyke et al., Toxicologist, 2010, 2011, 2012) in non-restrained animals. In the current study, we examined the abili...

  10. Exposure to Novelty Weakens Conditioned Fear in Long-Evans Rats

    ERIC Educational Resources Information Center

    Anderson, Matthew J.; Burpee, Tara E.; Wall, Matthew J.; McGraw, Justin J.

    2013-01-01

    The present study sought to determine whether post-training exposure to a novel or familiar object, encountered in either the location of the original fear conditioning (black compartment of a passive avoidance {PA} chamber) or in a neutral setting (open field where initial object training had occurred) would prove capable of reducing fear at…

  11. BEHAVIORAL ASSESSMENTS OF LONG EVANS RATS FOLLOWING A 13 WEEK SUBCHRONIC TOLUENE EXPOSURE.

    EPA Science Inventory

    Whereas the acute effects of volatile organic compounds (VOCs) are relatively well understood, there is some controversy regarding the potential for persistent effects following long-term exposure. The current study sought to develop an animal model of subchronic exposure to VOCs...

  12. Effects produced by single and repeated dosages of Fipronil on the EEG of Long Evans Rats

    EPA Science Inventory

    We have previously reported that various classes of pesticides have different effects on the non- stimulus driven EEG after acute treatment, including fipronil (25 or 50 mg/kg) (Lyke et a!., Toxicologist, 2010, 2011, 2012, 2013). In this study, we compared the effects of single a...

  13. Developmental neurotoxicity of PHAHs: Endocrine-mediated and general behavioral endpoints in adult male rats.

    PubMed

    Lilienthal, Hellmuth; Roth-Härer, Astrid; Hack, Alfons; Altmann, Lilo; Winneke, Gerhard

    2005-05-01

    During development, gonadal steroids exert effects on the nervous system which are long-lasting or organizational, in contrast to the transient activational actions in adulthood. Therefore, disturbance of neuroendocrine functions by developmental exposure to polyhalogenated aromatic hydrocarbons (PHAHs) is likely to affect sex-dependent behavior in adults. Our previous data revealed effects of maternal PCB exposure on sexual differentiation of the brain and subsequent sweet preference as sexually dimorphic behavior in adult offspring. Present research is focused on brominated flame retardants because of their wide-spread use and accumulation in human breast milk. Pregnant Long Evans rats were SC injected with PBDE 99 (2,2',4,4',5-PBDE) daily from gestational day 10 to 18. For comparison, an additional group was exposed to Aroclor 1254. Preliminary results indicate a dose-related increase in sweet preference in adult male offspring exposed to PBDE. Exposure also led to decreases in testosterone and estradiol serum levels. Additional decreases were detected in male anogenital distance. There were no changes of locomotor activity in the open field. On haloperidol-induced catalepsy, latencies were prolonged in all exposed males. In summary, PBDE induced endocrine effects and concomitant changes of sex-dependent behavior similar to PCBs. Outcome of general behavior suggests an involvement of dopaminergic processes in developmental PBDE exposure.

  14. q-Space diffusion MRI (QSI) of the disease progression in the spinal cords of the Long Evans shaker: diffusion time and apparent anisotropy

    PubMed Central

    Anaby, Debbie; Duncan, Ian D.; Smith, Chelsey M.; Cohen, Yoram

    2014-01-01

    q-Space diffusion MRI (QSI) was used to study the spinal cords of Long Evans shaker (les) rats, a model of dysmyelination, and their age-matched controls at different maturation stages. Diffusion was measured parallel and perpendicular to the fibers of the spinal cords of the two groups and at different diffusion times. The results showed that QSI is able to detect the dysmyelination process that occurs in this model in the different stages of the disease. The differences in the diffusion characteristics of the spinal cords of the two groups were found to be larger when the diffusion time was increased from 22 to 100 ms. We found that the radial mean displacement is a much better parameter than the QSI fractional anisotropy (FA) to document the differences between the two groups. We observed that the degree of myelination affects the diffusion characteristics of the tissues, but has a smaller effect on FA. All of the extracted diffusion parameters that are affected by the degree of myelination are affected in a diffusion time-dependent fashion, suggesting that the terms apparent anisotropy, apparent fractional anisotropy and even apparent root-mean-square displacement (rmsD) are more appropriate. PMID:24123305

  15. Central amygdala lesions inhibit pontine nuclei acoustic reactivity and retard delay eyeblink conditioning acquisition in adult rats.

    PubMed

    Pochiro, Joseph M; Lindquist, Derick H

    2016-06-01

    In delay eyeblink conditioning (EBC) a neutral conditioned stimulus (CS; tone) is repeatedly paired with a mildly aversive unconditioned stimulus (US; periorbital electrical shock). Over training, subjects learn to produce an anticipatory eyeblink conditioned response (CR) during the CS, prior to US onset. While cerebellar synaptic plasticity is necessary for successful EBC, the amygdala is proposed to enhance eyeblink CR acquisition. In the current study, adult Long-Evans rats received bilateral sham or neurotoxic lesions of the central nucleus of the amygdala (CEA) followed by 1 or 4 EBC sessions. Fear-evoked freezing behavior, CS-mediated enhancement of the unconditioned response (UR), and eyeblink CR acquisition were all impaired in the CEA lesion rats relative to sham controls. There were also significantly fewer c-Fos immunoreactive cells in the pontine nuclei (PN)-major relays of acoustic information to the cerebellum-following the first and fourth EBC session in lesion rats. In sham rats, freezing behavior decreased from session 1 to 4, commensurate with nucleus-specific reductions in amygdala Fos+ cell counts. Results suggest delay EBC proceeds through three stages: in stage one the amygdala rapidly excites diffuse fear responses and PN acoustic reactivity, facilitating cerebellar synaptic plasticity and the development of eyeblink CRs in stage two, leading, in stage three, to a diminution or stabilization of conditioned fear responding.

  16. Hypertension during chronic exposure to cold: Comparison between Sprague Dawley (SD) and Long Evans (LE) strains

    SciTech Connect

    Riesselmann, A.; Baron, A.; Fregly, M.J. )

    1991-03-11

    Hypertension accompanies chronic exposure of SD rats to cold (5-6C), including elevation of systolic, diastolic, and mean blood pressures and cardiac hypertrophy. The renin-angiotensin system may play an important role. Earlier studies suggested that the LE strain may have a decrease in angiotensin I converting enzyme (ACE) activity. Measurement of ACE activity in plasmas of SE and LE strains revealed that basal activity of ACE in the plasma of the LE strain was significantly less than that of the SD strain. A second study was carried out in which both strains were exposed to cold for 7 weeks. There were clear differences between strains. Rats of the SD strain had a significant elevation in their blood pressure; a significantly increased urinary output of norepinephrine (NE) and epinephrine (E); and significant increases in weights of heart, kidneys, adrenals, and brown adipose tissue (IBAT) compared to their controls maintained at 26C. In contrast, rats of the LE strain were less responsive to cold in that blood pressure failed to rise as sharply and to attain as high a level; NE and E outputs, as well as weights of heart and IBAT were significantly less than those of rats of the cold-treated SD strain. Thus, the lower ACE activity in plasma of LE strain, as well as a reduced secretion of catecholamines, may protect these rats against the rise of blood pressure characteristically observed when rats of the SD strain are exposed to cold.

  17. Effects of perinatal bisphenol A exposure during early development on radial arm maze behavior in adult male and female rats

    PubMed Central

    Sadowski, Renee N.; Park, Pul; Neese, Steven L.; Ferguson, Duncan C.; Schantz, Susan L.; Juraska, Janice M.

    2014-01-01

    Previous work has shown that exposure to bisphenol A (BPA) can affect anxiety behavior. However, no studies have examined whether administration of this endocrine disruptor during the perinatal period has the potential to induce alterations in cognitive behavior in both adult males and females as assessed in an appetitive task. The goal of the current study was to determine whether exposure to different doses of BPA during early development alters performance on the 17-arm radial maze in adulthood in Long-Evans rats. Oral administration of corn oil (vehicle), 4 μg/kg, 40 μg/kg, or 400 μg/kg BPA to the dams occurred daily throughout pregnancy, and the pups received direct oral administration of BPA between postnatal days 1-9. Blood was collected from offspring at weaning age to determine levels of several hormones (thyroxine, thyroid stimulating hormone, follicle stimulating hormone, luteinizing hormone). One male and one female from each litter were evaluated on the 17-arm radial maze, a working/reference memory task, in adulthood. Results indicated that after exposure to BPA at both 4 and 400 μg/kg/day, rats of both sexes had decreased levels of FSH at weaning. There were no significant effects of BPA on performance on the radial arm maze in males or females. In conclusion, exposure to BPA during early development had modest effects on circulating hormones but did not affect a spatial learning and memory task. PMID:24440629

  18. Adolescent rats are more prone to binge eating behavior: a study of age and obesity as risk factors.

    PubMed

    Bekker, Liza; Barnea, Royi; Brauner, Akiva; Weller, Aron

    2014-08-15

    Binge eating (BE) is characterized by repeated, intermittent over-consumption of food in a brief period of time. This study aims to advance the understanding of potential risk factors for BE such as obesity, overeating and adolescence as an age group. We used the Otsuka Long Evans Tokushima Fatty (OLETF) rat, a genetic overeating-induced obesity model with increased preferences for sweet and fat. Adolescent and adult rats from both strains (OLETF and the lean control strain, Long Evans Tokushima Otsuka [LETO]) received limited access to a palatable liquid diet (Ensure vanilla) for three weeks. Water and chow were available throughout the study, but access to Ensure was limited to two hours, three times a week (3TW group) or every work day (5TW group). As expected, OLETF rats consumed more Ensure and were more BE-prone (BEP) than LETO rats at both ages. Adolescent rats showed a significantly larger binge size as demonstrated by a greater increase in Ensure intake, compared to adults. Furthermore, while the adults reduced their chow intake, compensating for increased Ensure intake, the adolescents increased their chow intake too. Finally, the adolescent rats showed binge like behavior earlier in the study and they tended to be BEP more than the adults. Our findings in rats suggest that adolescents and in particular obese adolescents are at risk for BE, and BE can lead to overweight, thus providing the basis for examination of biological mechanisms of this process in animal models. PMID:24815316

  19. Neonatal treatment with lipopolysaccharide differentially affects adult anxiety responses in the light-dark test and taste neophobia test in male and female rats.

    PubMed

    Tenk, Christine M; Kavaliers, Martin; Ossenkopp, Klaus-Peter

    2013-05-01

    Neonatal administration of the bacterial cell wall component, lipopolysaccharide (LPS) has been shown to alter a variety of behavioural and physiological processes in the adult rat, including altering adult anxiety-like behaviour. Research conducted to date, however, has produced conflicting findings with some results demonstrating increases in adult anxiety-like behaviour while others report decreases or no changes in anxiety-like behaviour. Thus, the current study conducted additional evaluation of the effects of neonatal LPS exposure on adult anxiety-like behaviours by comparing the behavioural outcomes in the more traditional light-dark test, together with the less common hyponeophagia to sucrose solution paradigm. Male and female Long-Evans rats were treated systemically with either LPS (50μg/kg) or saline (0.9%) on postnatal days 3 and 5. Animals were then tested in the light-dark apparatus on postnatal day 90 for 30min. Next, following 5 days of habituation to distilled water delivery in Lickometer drinking boxes, animal were tested for neophagia to a 10% sucrose solution (0.3M) for 30min daily on postnatal days 96 and 97. In the light-dark test, neonatal LPS treatment decreased adult anxiety-like behaviour in females, but not males. In contrast, neonatal exposure to LPS did not influence adult anxiety-like behaviour as measured by hyponeophagia, but altered the licking patterns of drinking displayed towards a novel, palatable sucrose solution in adult males and females, in a manner that may reflect a decrease in situational anxiety. The current study supports the idea that neonatal LPS treatment results in highly specific alterations of adult anxiety-like behaviour, the nature of which seems to depend not only on the measure of anxiety behaviour used, but also possibly, on the degree of anxiety experienced during the behavioural test.

  20. Subchronic Toluene Exposure alters Retinal Function in Long Evans Rats: Experimental Evidence Supporting Observations from Studies of Exposed Humans.

    EPA Science Inventory

    Studies of humans chronically exposed to volatile organic solvents commonly report impaired visual functions, including low contrast sensitivity and reduced color discrimination. These reports have been controversial, however, in part due to a lack of confirmation from controlled...

  1. ELECTRORETINOGRAMS ARE ALTERED BY SUBCHRONIC TOLUENE EXPOSURE TO LONG EVANS RATS: EXPERIMENTAL EVIDENCE SUPPORTING OBSERVATIONS FROM STUDIES OF EXPOSED HUMANS

    EPA Science Inventory

    Impaired visual functions, including low contrast sensitivity and reduced color discrimination, have been reported in studies of humans chronically exposed to several volatile organic solvents. These reports remain controversial, however, in part due to a lack of confirmation fro...

  2. Acute and Subchronic Toxicity of Inhaled Toluene in Male Long-Evans Rats: Oxidative Stress Markers in Brain

    EPA Science Inventory

    The effects of exposure to volatile organic compounds (VOCs), which are of concern to the EPA, are poorly understood, in part because of insufficient characterization of how human exposure duration impacts VOC effects. Two inhalation studies with multiple endpoints, one acute an...

  3. RELATIONSHIPS BETWEEN TISSUE LEVELS OF CARBARYL, A PROTOTYPICAL CARBAMATE PESTICIDE, AND CHOLINESTERASE INHIBITION IN LONG EVANS RATS.

    EPA Science Inventory

    As part of an effort to link pharmacokinetics with biochemical and physiological endpoints, the relationships between cholinesterase (ChE) activity and tissue levels of a prototypical N-methyl carbamate pesticide were examined. In a dose-response study, carbaryl (0, 3, 7.5, 15, 3...

  4. Effects of lateral hypothalamic lesion with the neurotoxin hypocretin-2-saporin on sleep in Long-Evans rats.

    PubMed

    Gerashchenko, D; Blanco-Centurion, C; Greco, M A; Shiromani, P J

    2003-01-01

    Narcolepsy, a disabling neurological disorder characterized by excessive daytime sleepiness, sleep attacks, sleep fragmentation, cataplexy, sleep-onset rapid eye movement sleep periods and hypnagogic hallucinations was recently linked to a loss of neurons containing the neuropeptide hypocretin. There is considerable variability in the severity of symptoms between narcoleptic patients, which could be related to the extent of neuronal loss in the lateral hypothalamus. To investigate this possibility, we administered two concentrations (90 ng or 490 ng in a volume of 0.5 microl) of the neurotoxin hypocretin-2-saporin, unconjugated saporin or saline directly to the lateral hypothalamus and monitored sleep, the entrained and free-running rhythm of core body temperature and activity. Neurons stained for hypocretin or for the neuronal specific marker were counted in the perifornical area, dorsomedial and ventromedial nucleus of the hypothalamus. More neuronal nuclei (NeuN) cells were destroyed by the higher concentration of hypocretin-2-saporin (-55%) compared with the lower concentration (-34%) in the perifornical area, although both concentrations lesioned the hypocretin neurons almost equally well (high concentration=91%; low concentration=88%). The high concentration of hypocretin-2-saporin also lesioned neurons in the dorsomedial nucleus of the hypothalamus and ventromedial nucleus of the hypothalamus. Narcoleptic-like sleep behavior was produced by both concentrations of the hypocretin-2-saporin. The high concentration produced a larger increase in non-rapid eye movement sleep amounts during the normally active night cycle than low concentration. Neither concentration of hypocretin-2-saporin disrupted the phase or period of the core temperature or activity rhythms. The low concentration of unconjugated saporin did not significantly lesion hypocretin or neurons and did not alter sleep. The high concentration of unconjugated saporin produced some loss of neuronal nuclei-immunoreactive (NeuN-ir) neurons and hypocretin immunoreactive neurons, but only a transient increase in non-rapid eye movement sleep. These results led us to conclude that the extent of hypocretin neuronal loss together with an accompanying loss of cells in the lateral hypothalamus may explain the differences in severity of symptoms seen in human narcolepsy.

  5. INHIBITION OF BRAIN CHOLINESTERASE AND THE PHOTIC AFTER DISCHARGE OF FLASH EVOKED POTENTIALS PRODUCED BY CARBARYL IN LONG EVANS RATS.

    EPA Science Inventory

    Carbaryl is a widely used N-methyl carbamate pesticide that acts by inhibiting cholinesterases (ChE), which may lead to cholinergic toxicity. Flash evoked potentials (FEPs) are a neurophysiological response often used to detect central nervous system (CNS) changes following expos...

  6. Neurodevelopmental malformations of the cerebellar vermis in genetically engineered rats

    EPA Science Inventory

    The cerebellar vermis is particularly vulnerable to neurodevelopmental malformations in humans and rodents. Sprague-Dawley, and Long-Evans rats exhibit spontaneous cerebellar malformations consisting of heterotopic neurons and glia in the molecular layer of the vermis. Malformati...

  7. In utero/lactational and adult exposures to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) show differential effects on craniofacial development and growth in rats.

    PubMed

    Sholts, Sabrina B; Korkalainen, Merja; Simanainen, Ulla; Miettinen, Hanna M; Håkansson, Helen; Viluksela, Matti

    2015-11-01

    In a previous study of female Han/Wistar (H/W) and Long-Evans (L-E) rats, we found that adult exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was associated with size decreases in the cranium and especially the face. In this study we compared these crania to those from male and female Sprague-Dawley (S-D) rats with in utero/lactational exposure to TCDD, using morphometric variables of size, shape, and fluctuating asymmetry to quantify the effects of dose on craniofacial development and growth. At the highest levels of exposure, in utero/lactational and adult TCDD exposures both resulted in small but significant reductions in facial size parameters (i.e., 3-5%) in only females and minor effects on facial shape in both sexes. The shape effects of in utero/lactational exposure were most significant at the sutural intersections, whereas adult exposure to TCDD corresponded to dose-dependent changes of decreasing facial length and vault breadth. Fluctuating asymmetry in general explained a relatively small amount of shape variation compared with other effects, and only increased significantly in female L-E rats with high levels of adult exposure to TCDD. These results indicate that TCDD-related changes in cranial development and growth in rats can vary with the timing and duration of exposure, and with sex. Further investigations of other dioxin-like compounds and animal species will broaden our understanding of how chemicals exposure can influence the development and growth of the mammalian skeleton.

  8. Early life versus lifelong oral manganese exposure differently impairs skilled forelimb performance in adult rats.

    PubMed

    Beaudin, Stephane A; Nisam, Sean; Smith, Donald R

    2013-01-01

    Recent studies of children suggest that exposure to elevated manganese (Mn) levels disrupts aspects of motor, cognitive and behavioral functions that are dependent on dopamine brain systems. Although basal ganglia motor functions are well-known targets of adult occupational Mn exposure, the extent of motor function deficits in adults as a result of early life Mn exposure is unknown. Here we used a rodent model early life versus lifelong oral Mn exposure and the Montoya staircase test to determine whether developmental Mn exposure produces long-lasting deficits in sensorimotor performance in adulthood. Long-Evans male neonate rats (n=11/treatment) were exposed daily to oral Mn at levels of 0, 25, or 50mg Mn/kg/d from postnatal day (PND) 1-21 (early life only), or from PND 1-throughout life. Staircase testing began at age PND 120 and lasted 1month to objectively quantify measures of skilled forelimb use in reaching and pellet grasping/retrieval performance. Behavioral reactivity also was rated on each trial. Results revealed that (1) behavioral reactivity scores were significantly greater in the Mn-exposed groups, compared to controls, during the staircase acclimation/training stage, but not the latter testing stages, (2) early life Mn exposure alone caused long-lasting impairments in fine motor control of reaching skills at the higher, but not lower Mn dose, (3) lifelong Mn exposure from drinking water led to widespread impairment in reaching and grasping/retrieval performance in adult rats, with the lower Mn dose group showing the greatest impairment, and (4) lifelong Mn exposure produced similar (higher Mn group) or more severe (lower Mn group) impairments compared to their early life-only Mn exposed counterparts. Collectively, these results substantiate the emerging clinical evidence in children showing associations between environmental Mn exposure and deficits in fine sensorimotor function. They also show that the objective quantification of skilled motor

  9. Anabolic-androgenic steroid effects on sexual receptivity in ovariectomized rats.

    PubMed

    Blasberg, M E; Clark, A S

    1997-12-01

    Anabolic-androgenic steroid (AAS) compounds are synthetic androgens taken by athletes to increase physical strength and endurance. Recent studies in our laboratory have demonstrated that AAS administration disrupts the estrous cycle of Long-Evans rats. The present experiments examined the effects of six commonly abused AAS compounds on sexual receptivity in ovariectomized rats. Adult female Long-Evans rats received estradiol benzoate (EB; 2.0 micrograms/day s.c.) for 6 consecutive days followed by 15 days of EB concurrent with daily s.c. injections of 7.5 mg/kg of one of the following AAS compounds: 17 alpha-methyltestosterone, methandrostenolone, nandrolone decanoate, stanozolol, oxymetholone, testosterone cypionate, or the oil vehicle. On Day 15, all female rats received progesterone (1.0 mg/rat) 4 h before testing. Tests for sexual receptivity were conducted on Days 3, 6, 14, and 15 of AAS treatment. Although the time course of AAS effects on sexual receptivity varied, some overall effects were clear. For example, 17 alpha-methyltestosterone, methandrostenolone, nandrolone decanoate, and stanozolol interfered with the display of sexual receptivity on Day 14, whereas oxymetholone and testosterone cypionate had no effect. Rats in all groups displayed high levels of sexual receptivity after receiving progesterone on Day 15. Our results show that AAS compounds vary in their degree of inhibition of female sexual behavior in ovariectomized rats. PMID:9454671

  10. Anabolic-androgenic steroid effects on sexual receptivity in ovariectomized rats.

    PubMed

    Blasberg, M E; Clark, A S

    1997-12-01

    Anabolic-androgenic steroid (AAS) compounds are synthetic androgens taken by athletes to increase physical strength and endurance. Recent studies in our laboratory have demonstrated that AAS administration disrupts the estrous cycle of Long-Evans rats. The present experiments examined the effects of six commonly abused AAS compounds on sexual receptivity in ovariectomized rats. Adult female Long-Evans rats received estradiol benzoate (EB; 2.0 micrograms/day s.c.) for 6 consecutive days followed by 15 days of EB concurrent with daily s.c. injections of 7.5 mg/kg of one of the following AAS compounds: 17 alpha-methyltestosterone, methandrostenolone, nandrolone decanoate, stanozolol, oxymetholone, testosterone cypionate, or the oil vehicle. On Day 15, all female rats received progesterone (1.0 mg/rat) 4 h before testing. Tests for sexual receptivity were conducted on Days 3, 6, 14, and 15 of AAS treatment. Although the time course of AAS effects on sexual receptivity varied, some overall effects were clear. For example, 17 alpha-methyltestosterone, methandrostenolone, nandrolone decanoate, and stanozolol interfered with the display of sexual receptivity on Day 14, whereas oxymetholone and testosterone cypionate had no effect. Rats in all groups displayed high levels of sexual receptivity after receiving progesterone on Day 15. Our results show that AAS compounds vary in their degree of inhibition of female sexual behavior in ovariectomized rats.

  11. Augmenting saturated LTP by broadly spaced episodes of theta-burst stimulation in hippocampal area CA1 of adult rats and mice

    PubMed Central

    Cao, Guan

    2014-01-01

    Hippocampal long-term potentiation (LTP) is a model system for studying cellular mechanisms of learning and memory. Recent interest in mechanisms underlying the advantage of spaced over massed learning has prompted investigation into the effects of distributed episodes of LTP induction. The amount of LTP induced in hippocampal area CA1 by one train (1T) of theta-burst stimulation (TBS) in young Sprague-Dawley rats was further enhanced by additional bouts of 1T given at 1-h intervals. However, in young Long-Evans (LE) rats, 1T did not initially saturate LTP. Instead, a stronger LTP induction paradigm using eight trains of TBS (8T) induced saturated LTP in hippocampal slices from both young and adult LE rats as well as adult mice. The saturated LTP induced by 8T could be augmented by another episode of 8T following an interval of at least 90 min. The success rate across animals and slices in augmenting LTP by an additional episode of 8T increased significantly with longer intervals between the first and last episodes, ranging from 0% at 30- and 60-min intervals to 13–66% at 90- to 180-min intervals to 90–100% at 240-min intervals. Augmentation above initially saturated LTP was blocked by the N-methyl-d-aspartate (NMDA) glutamate receptor antagonist d-2-amino-5-phosphonovaleric acid (d-APV). These findings suggest that the strength of induction and interval between episodes of TBS, as well as the strain and age of the animal, are important components in the augmentation of LTP. PMID:25057146

  12. α- and β-Adrenergic receptors differentially modulate the emission of spontaneous and amphetamine-induced 50-kHz ultrasonic vocalizations in adult rats.

    PubMed

    Wright, Jennifer M; Dobosiewicz, May R S; Clarke, Paul B S

    2012-02-01

    Amphetamine (AMPH) increases adult rat 50-kHz ultrasonic vocalizations, preferentially promoting frequency-modulated (FM) calls that have been proposed to reflect positive affect. The main objective of this study was to investigate a possible noradrenergic contribution to AMPH-induced calling. Adult male Long-Evans rats were tested with AMPH (1 mg/kg intraperitoneal) or saline combined with various systemic pretreatments: clonidine (α2 adrenergic agonist), prazosin (α1 antagonist), atipamezole (α2 antagonist), propranolol, betaxolol, and/or ICI 118,551 (β1/β2, β1, and β2 antagonists, respectively), nadolol (β1/β2 antagonist, peripheral only), or NAD-299 (5HT(1A) antagonist). In addition, effects of cirazoline (α1 adrenergic agonist) and cocaine (0.25-1.5 mg/kg intravenous) were studied alone. AMPH-induced calling was suppressed by low-dose clonidine and prazosin. Cirazoline and atipamezole did not significantly affect calling rate. Propranolol, without affecting the call rate, dose dependently promoted 'flat' calls under AMPH while suppressing 'trills,' thus reversing the effects of AMPH on the 'call subtype profile.' This effect of propranolol seemed to be mediated by simultaneous inhibition of CNS β1 and β2 rather than by 5HT(1A) receptors. Finally, cocaine elicited fewer calls than did AMPH, but produced the same shift in the call subtype profile. Taken together, these results reveal differential drug effects on flat vs trill vs other FM 50-kHz calls. These findings highlight the value of detailed call subtype analyses, and show that 50-kHz calls are associated with adrenergic α1- and β-receptor mechanisms. These preclinical findings suggest that noradrenergic contributions to psychostimulant subjective effects may warrant further investigation.

  13. α- and β-Adrenergic Receptors Differentially Modulate the Emission of Spontaneous and Amphetamine-Induced 50-kHz Ultrasonic Vocalizations in Adult Rats

    PubMed Central

    Wright, Jennifer M; Dobosiewicz, May R S; Clarke, Paul B S

    2012-01-01

    Amphetamine (AMPH) increases adult rat 50-kHz ultrasonic vocalizations, preferentially promoting frequency-modulated (FM) calls that have been proposed to reflect positive affect. The main objective of this study was to investigate a possible noradrenergic contribution to AMPH-induced calling. Adult male Long-Evans rats were tested with AMPH (1 mg/kg intraperitoneal) or saline combined with various systemic pretreatments: clonidine (α2 adrenergic agonist), prazosin (α1 antagonist), atipamezole (α2 antagonist), propranolol, betaxolol, and/or ICI 118,551 (β1/β2, β1, and β2 antagonists, respectively), nadolol (β1/β2 antagonist, peripheral only), or NAD-299 (5HT1A antagonist). In addition, effects of cirazoline (α1 adrenergic agonist) and cocaine (0.25–1.5 mg/kg intravenous) were studied alone. AMPH-induced calling was suppressed by low-dose clonidine and prazosin. Cirazoline and atipamezole did not significantly affect calling rate. Propranolol, without affecting the call rate, dose dependently promoted ‘flat' calls under AMPH while suppressing ‘trills,' thus reversing the effects of AMPH on the ‘call subtype profile.' This effect of propranolol seemed to be mediated by simultaneous inhibition of CNS β1 and β2 rather than by 5HT1A receptors. Finally, cocaine elicited fewer calls than did AMPH, but produced the same shift in the call subtype profile. Taken together, these results reveal differential drug effects on flat vs trill vs other FM 50-kHz calls. These findings highlight the value of detailed call subtype analyses, and show that 50-kHz calls are associated with adrenergic α1- and β-receptor mechanisms. These preclinical findings suggest that noradrenergic contributions to psychostimulant subjective effects may warrant further investigation. PMID:22030713

  14. Acute effects of aspartame on aggression and neurochemistry of rats.

    PubMed

    Goerss, A L; Wagner, G C; Hill, W L

    2000-08-01

    The inverse relationship between serotonin and aggression was investigated in rats treated with aspartame, a sweetener thought to interfere with the synthesis of this neurotransmitter. Eleven adult, male Long-Evans rats received either aspartame (200-800 mg/kg, IP) or the vehicle prior to testing in a standard resident-intruder paradigm. Contrary to our hypothesis, aspartame significantly decreased aggression as shown by increased latencies to the first attack and decreased number of bites per session. Corresponding with the effects on aggression, aspartame significantly increased striatal levels of serotonin. It was concluded that high doses of aspartame reduced aggressive attack via a serotonergic mechanism while the lower dose was without effect on either variable.

  15. Increased atrial natriuretic peptide (6-33) binding sites in the subfornical organ of water deprived and Brattleboro rats

    SciTech Connect

    Saavedra, J.M.; Israel, A.; Correa, F.M.A.; Kurihara, M.

    1986-09-01

    Binding sites for rat atrial natriuretic eptide (6-33) (ANP) were quantitated in the subfornical organ of chronically dehydrated homozygous Brattleboro rats unable to synthesize vasopressin; heterozygous Brattleboro rats, their controls, Long Evans rats and Long Evans rats after 4 days of water deprivation. Brain sections were incubated in the presence of /sup 125/I-ANP and the results analyzed by autoradiography coupled to computerized microdensitometry and comparison to /sup 125/I-standards. Brattleboro rats and water deprived Long Evans rats presented a higher number of ANP binding sites than their normally hydrated controls. The results suggest a role of ANP binding sites in the subfornical organ in the central regulation of fluid balance and vasopressin secretion.

  16. Interactions between respiratory oscillators in adult rats

    PubMed Central

    Huckstepp, Robert TR; Henderson, Lauren E; Cardoza, Kathryn P; Feldman, Jack L

    2016-01-01

    Breathing in mammals is hypothesized to result from the interaction of two distinct oscillators: the preBötzinger Complex (preBötC) driving inspiration and the lateral parafacial region (pFL) driving active expiration. To understand the interactions between these oscillators, we independently altered their excitability in spontaneously breathing vagotomized urethane-anesthetized adult rats. Hyperpolarizing preBötC neurons decreased inspiratory activity and initiated active expiration, ultimately progressing to apnea, i.e., cessation of both inspiration and active expiration. Depolarizing pFL neurons produced active expiration at rest, but not when inspiratory activity was suppressed by hyperpolarizing preBötC neurons. We conclude that in anesthetized adult rats active expiration is driven by the pFL but requires an additional form of network excitation, i.e., ongoing rhythmic preBötC activity sufficient to drive inspiratory motor output or increased chemosensory drive. The organization of this coupled oscillator system, which is essential for life, may have implications for other neural networks that contain multiple rhythm/pattern generators. DOI: http://dx.doi.org/10.7554/eLife.14203.001 PMID:27300271

  17. Atomoxetine facilitates Attentional Set Shifting in adolescent rats

    PubMed Central

    Cain, Rachel E.; Wasserman, Michelle C.; Waterhouse, Barry D.; McGaughy, Jill A.

    2011-01-01

    Adolescent rats show immaturities in executive function and are less able than adult rats to learn reinforcement reversals and shift attentional set. These two forms of executive function rely on the functional integrity of the orbitofrontal and prelimbic cortices respectively. Drugs used to treat attention deficit disorder, such as atomoxetine, that increase cortical catecholamine levels improve executive functions in humans, non-human primates and adult rats with prefrontal lesions. Cortical noradrenergic systems are some of the last to mature in primates and rats. Moreover, norepinephrine transporters (NET) are higher in juvenile rats than adults. The underdeveloped cortical noradrenergic system and higher number of NET are hypothesized to underlie the immaturities in executive function found in adolescents. We assessed executive function in male Long-Evans rats using an intra-dimensional/extra-dimensional set shifting task. We administered the NET blocker, atomoxetine (0.0, 0.1, 0.9 mg/kg/ml; i.p.), prior to the test of attentional set shift and a reinforcement reversal. The lowest dose of drug facilitated attentional set shifting but had no effect on reversal learning. These data demonstrate that NET blockade allows adolescent rats to more easily perform attentional set shifting. PMID:21927630

  18. Spatial and visual discrimination reversals in adult and geriatric rats exposed during gestation to methylmercury and n-3 polyunsaturated fatty acids

    PubMed Central

    Paletz, Elliott M.; Day, Jeremy J.; Craig-Schmidt, Margaret C.; Newland, M. Christopher

    2007-01-01

    Fish contain essential long chain polyunsaturated fatty acids (PUFAs), particularly docosahexaenoic acid (DHA), an omega-3 (or n-3) PUFA, but are also the main source of exposure to methylmercury (MeHg), a potent developmental neurotoxicant. Since n-3 PUFAs support neural development and function, benefits deriving from a diet rich in n-3s have been hypothesized to protect against deleterious effects of gestational MeHg exposure. To determine whether protection occurs at the behavioral level, female Long-Evans rats were exposed, in utero, to 0, 0.5, or 5 ppm of Hg as MeHg via drinking water, approximating exposures of 0, 40, and 400 μg Hg/kg/day and producing 0, 0.29, and 5.50 ppm of total Hg in the brains of siblings at birth. They also received pre- and postnatal exposure to one of two diets, both based on the AIN-93 semipurified formulation. A “fish-oil” diet was high in, and a “coconut-oil” diet was devoid of, DHA. Diets were approximately equal in α-linolenic acid and n-6 PUFAs. As adults, the rats were first assessed with a spatial discrimination reversal (SDR) procedure and later with a visual (nonspatial) discrimination reversal (VDR) procedure. MeHg increased the number of errors to criterion for both SDR and VDR during the first reversal, but effects were smaller or nonexistent on the original discrimination and on later reversals. No such MeHg-related deficits were seen when the rats were retested on SDR after two years of age. These results are consistent with previous reports and hypotheses that gestational MeHg exposure produces perseverative responding. No interactions between Diet and MeHg were found, suggesting that n-3 PUFAs do not guard against these behavioral effects. Brain Hg concentrations did not differ between the diets, either. In geriatric rats, failures to respond were less common and response latencies were shorter for rats fed the fish oil diet, suggesting that exposure to a diet rich in n-3s may lessen the impact of age

  19. Differences between brainstem gliomas in juvenile and adult rats

    PubMed Central

    WANG, YU; TIAN, YONGJI; WAN, HONG; LI, DEZHI; WU, WENHAO; YIN, LUXIN; JIANG, JIAN; WAN, WEIQING; ZHANG, LIWEI

    2013-01-01

    Clinical studies have shown that gliomas of the brainstem behave differently in children and adults. The aim of the present study was to compare and analyze the differences between these gliomas in juvenile and adult rats with regard to tumor growth, survival, pathology and magnetic resonance imaging (MRI). A total of 25 juvenile and 25 adult Wistar rats were divided into groups A (15 juvenile rats), B (10 juvenile rats), C (15 adult rats) and D (10 adult rats). The rats of groups A and C (experimental) were injected with glioma cells, while groups B and D (control) were injected with a physiological saline solution. Rat neurological signs, survival time, tumor size, hematoxylin and eosin (HE) staining and immunohistochemical staining for MMP-2, MMP-9 and β-catenin were compared. The survival time of group A was 19.47±2.232 days, whereas that of group C was 21.47±2.232 days (P<0.05). The tumor sizes were 4.55 and 4.62 mm (P>0.05) in groups A and C, respectively. HE and immunohistochemical staining revealed no differences between the groups. The results suggest that the growth patterns and invasiveness of brainstem gliomas may vary in children compared with adults due to the varied biological behaviors of the tumor cells. PMID:23946812

  20. Time course of cholinesterase inhibition in adult rats treated acutely with carbaryl, carbofuran, formetanate, methomyl, methiocarb, oxamyl or propoxur.

    PubMed

    Padilla, S; Marshall, R S; Hunter, D L; Lowit, A

    2007-03-01

    To compare the toxicity of seven N-methyl carbamates, time course profiles for brain and red blood cell (RBC) cholinesterase (ChE) inhibition were established for each. Adult, male, Long Evans rats (n=4-5 dose group) were dosed orally with either carbaryl (30 mg/kg in corn oil); carbofuran (0.5 mg/kg in corn oil); formetanate HCl (10 mg/kg in water); methomyl (3 mg/kg in water); methiocarb (25 mg/kg in corn oil); oxamyl (1 mg/kg in water); or propoxur (20 mg/kg in corn oil). This level of dosing produced at least 40% brain ChE inhibition. Brain and blood were taken from 0.5 to 24 h after dosing for analysis of ChE activity using two different methods: (1) a radiometric method which limits the amount of reactivation of ChE activity, and (2) a spectrophotometric method (Ellman method using traditional, unmodified conditions) which may encourage reactivation. The time of peak ChE inhibition was similar for all seven N-methyl carbamate pesticides: 0.5-1.0 h after dosing. By 24 h, brain and RBC ChE activity in all animals returned to normal. The spectrophotometric method underestimated ChE inhibition. Moreover, there was a strong, direct correlation between brain and RBC ChE activity (radiometric assay) for all seven compounds combined (r(2)=0.73, slope 1.1), while the spectrophotometric analysis of the same samples showed a poor correlation (r(2)=0.09). For formetanate, propoxur, methomyl, and methiocarb, brain and RBC ChE inhibitions were not different over time, but for carbaryl, carbofuran and oxamyl, the RBC ChE was slightly more inhibited than brain ChE. These data indicate (1) the radiometric method is superior for analyses of ChE activity in tissues from carbamate-treated animals (2) that animals treated with these N-methyl carbamate pesticides are affected rapidly, and recover rapidly, and (3) generally, assessment of RBC ChE is an accurate predictor of brain ChE inhibition for these seven pesticides.

  1. Time course of cholinesterase inhibition in adult rats treated acutely with carbaryl, carbofuran, formetanate, methomyl, methiocarb, oxamyl or propoxur

    SciTech Connect

    Padilla, S. . E-mail: Padilla.Stephanie@epa.gov; Marshall, R.S. . E-mail: Marshall.renee@epa.gov; Hunter, D.L. . E-mail: Hunter.deborah@epa.gov; Lowit, A. . E-mail: Lowit.anna@epa.gov

    2007-03-15

    To compare the toxicity of seven N-methyl carbamates, time course profiles for brain and red blood cell (RBC) cholinesterase (ChE) inhibition were established for each. Adult, male, Long Evans rats (n = 4-5 dose group) were dosed orally with either carbaryl (30 mg/kg in corn oil); carbofuran (0.5 mg/kg in corn oil); formetanate HCl (10 mg/kg in water); methomyl (3 mg/kg in water); methiocarb (25 mg/kg in corn oil); oxamyl (1 mg/kg in water); or propoxur (20 mg/kg in corn oil). This level of dosing produced at least 40% brain ChE inhibition. Brain and blood were taken from 0.5 to 24 h after dosing for analysis of ChE activity using two different methods: (1) a radiometric method which limits the amount of reactivation of ChE activity, and (2) a spectrophotometric method (Ellman method using traditional, unmodified conditions) which may encourage reactivation. The time of peak ChE inhibition was similar for all seven N-methyl carbamate pesticides: 0.5-1.0 h after dosing. By 24 h, brain and RBC ChE activity in all animals returned to normal. The spectrophotometric method underestimated ChE inhibition. Moreover, there was a strong, direct correlation between brain and RBC ChE activity (radiometric assay) for all seven compounds combined (r {sup 2} = 0.73, slope 1.1), while the spectrophotometric analysis of the same samples showed a poor correlation (r {sup 2} = 0.09). For formetanate, propoxur, methomyl, and methiocarb, brain and RBC ChE inhibitions were not different over time, but for carbaryl, carbofuran and oxamyl, the RBC ChE was slightly more inhibited than brain ChE. These data indicate (1) the radiometric method is superior for analyses of ChE activity in tissues from carbamate-treated animals (2) that animals treated with these N-methyl carbamate pesticides are affected rapidly, and recover rapidly, and (3) generally, assessment of RBC ChE is an accurate predictor of brain ChE inhibition for these seven pesticides.

  2. Cocaine- and amphetamine-regulated transcript (CART) peptide immunoreactivity in feeding- and reward-related brain areas of young OLETF rats.

    PubMed

    Armbruszt, Simon; Abraham, Hajnalka; Figler, Maria; Kozicz, Tamas; Hajnal, Andras

    2013-05-01

    Cocaine- and amphetamine-regulated transcript (CART) peptide is expressed in brain areas involved in the control of appetite, drug reward and homeostatic regulation and it has an overall anorexigenic effect. Recently, we have shown that CART peptide immunoreactivity was significantly reduced in the rostral part of the nucleus accumbens and in the rostro-medial part of the nucleus of the solitary tract in adult CCK-1 receptor deficient obese diabetic Otsuka Long Evans Tokushima Fatty (OLETF) rats compared to Long Evans Tokushima Otsuka (LETO) lean controls. It is not clear, however, whether altered CART expression is caused primarily by the deficiency in CCK-1 signaling or whether is related to the obese and diabetic phenotype of the OLETF strain which develops at a later age. Therefore, in the present study, CART-immunoreaction in feeding-related areas of the brain was compared in young, age-matched (6-7 weeks old) non-obese, non-diabetic OLETF rats and in LETO controls. We found that, young, non-diabetic OLETF rats revealed unaltered distribution of CART-peptide expressing neurons and axons throughout the brain when compared to age-matched LETO rats. In contrast to previous results observed in the obese diabetic adult rats, intensity of CART immunoreaction did not differ in the areas related to control of food-intake and reward in the young OLETFs compared to young LETO rats. Our findings suggest that factors secondary to obesity and/or diabetes rather than impaired CCK-1 receptor signaling may contribute to altered CART expression in the OLETF strain. PMID:23545074

  3. Cocaine- and amphetamine-regulated transcript (CART) peptide immunoreactivity in feeding- and reward-related brain areas of young OLETF rats

    PubMed Central

    Armbruszt, Simon; Abraham, Hajnalka; Figler, Maria; Kozicz, Tamas; Hajnal, Andras

    2013-01-01

    Cocaine- and amphetamine regulated transcript (CART) peptide is expressed in brain areas involved in the control of appetite, drug reward and homeostatic regulation and it has an overall anorexigenic effect. Recently, we have shown that CART peptide immunoreactivity was significantly reduced in the rostral part of the nucleus accumbens and in the rostro-medial part of the nucleus of the solitary tract in adult CCK-1 receptor deficient obese diabetic Otsuka Long Evans Tokushima Fatty (OLETF) rats compared to Long Evans Tokushima Otsuka (LETO) lean controls. It is not clear, however, whether altered CART expression is caused primarily by the deficiency in CCK-1 signaling or whether is related to the obese and diabetic phenotype of the OLETF strain which develops at a later age. Therefore, in the present study, CART-immunoreaction in feeding-related areas of the brain was compared in young, age-matched (6-7 weeks old) non-obese, non-diabetic OLETF rats and in LETO controls. We found that, young, non-diabetic OLETF rats revealed unaltered distribution of CART-peptide expressing neurons and axons throughout the brain when compared to age-matched LETO rats. In contrast to previous results observed in the obese diabetic adult rats, intensity of CART immunoreaction did not differ in the areas related to control of food-intake and reward in the young OLETFs compared to young LETO rats. Our findings suggest that factors secondary to obesity and/or diabetes rather than impaired CCK-1 receptor signaling may contribute to altered CART expression in the OLETF strain. PMID:23545074

  4. MAMMARY GLAND DEVELOPMENT AS A SENSITIVE END-POINT FOLLOWING ACUTE PERNATAL EXPOSURE TO A LOW DOSE ATRAZINE METABOLITE MIXTURE IN FEMALE LONG EVANS RATS

    EPA Science Inventory

    In order to characterize the potential developmental effects of atrazine (ATR) metabolites at low doses, an environmentally-based mixture (EBM) of ATR and its metabolites hydroxyatrazine, diaminochlorotriazine, deethylatrazine, and deisopropylatrazine was formulated based on surv...

  5. Short-term exposure to triclosan decreases thyroxine in vivo via upregulation of hepatic catabolism in young long-evans rats

    EPA Science Inventory

    Triclosan (5-chloro-2-(2,4-dichlorophenoxy)phenol)is a chlorinated phenolic antibacterial compound used in consumer products. Structural similarity of triclosan to thyroid hormones, in vitro activation ofthe human pregnane X receptor (PXR) and induction of hepatic Phase I enzymes...

  6. DEVELOPMENT OF A PHYSIOLOGICALLY-BASED PHARMACOKINETIC (PBPK) MODEL FOR THE INHALATION OF 2,2,4-TRIMETHYLPENTANE (TMP) IN LONG EVANS RATS.

    EPA Science Inventory

    TMP (2,2,4-trimethylpentane,“isooctane”) is a colorless liquid used primarily in the alkylation of isobutene and butylene reactions to derive high-octane fuels. TMP is released in the environment through the manufacture, use, and disposal of products associated with the gasoline ...

  7. Development of an inhalation physiologically based pharmacokinetic (PBPK) model for 2,2, 4-trimethylpentane (TMP) in male Long-Evans rats using gas uptake experiments.

    EPA Science Inventory

    2,2,4-Trimethylpentane (TMP) is a volatile colorless liquid used primarily to increase the octane rating of combustible fuels. TMP is released in the environment through the manufacture, use, and disposal of products associated with the gasoline and petroleum industry. Short-term...

  8. SEXUALLY DIMORPHIC LORDOSIS BEHAVIOR IS MORE SENSITIVE TO DISRUPTION BY DEVELOPMENTAL EXPOSURE TO ETHINYL ESTRADIOL THAN IS REPRODUCTIVE MORPHOLOGY IN THE LONG EVANS FEMALE RAT.

    EPA Science Inventory

    Anthropogenic estrogens are pervasive in the environment. Although the effects of these xenoestrogens are controversial in humans, some fish species are adversely affected in contaminated ecosystems. While studies investigating endocrine disruptors typically focus on reproducti...

  9. ANALYSIS OF PRENEOPLASTIC AND NEOPLASTIC RENAL LESIONS IN TSC2 MUTANT LONG-EVANS (EKER) RATS FOLLOWING EXPOSURE TO A MIXTURE OF DRINKING WATER DISINFECTION BY-PRODUCTS

    EPA Science Inventory

    Abstract

    Disinfection of surface water for human consumption results in the generation of a complex mixture of chemicals in potable water. Cancer risk assessment methodology assumes additivity of carcinogenic effects in the regulation of mixtures. A rodent model of ...

  10. TREATMENT OF LONG-EVANS RATS WITH A DEFINED MIXTURE OF DRINKING WATER DISINFECTION BY-PRODUCTS IMPACTS INTESTINAL MICROBIAL METABOLISM.

    EPA Science Inventory

    Water treatment results in the production of numerous halogenated disinfection by-products (DBPs), and has been associated with human colorectal cancer. Because the intestinal microbiota can bioactivate promutagens and procarcinogens, several studies have been done to examine the...

  11. THE CARCINOGENIC RESPONSE OF TSC2 MUTANT LONG EVANS (EKER) RATS TO A MIXTURE OF DRINKING WATER DISINFECTION BY-PRODUCTS WAS LESS THAN ADDITIVE

    EPA Science Inventory

    Cancer risk assessment methods for chemical mixtures in drinking water are not well defined. Current default risk assessments for chemical mixtures assume additivity of carcinogenic effects but this may not represent the actual biological response. A rodent model of hereditary ...

  12. PERINATAL EXPOSURE TO POLYCHLORINATED BIPHENYLS AROCLOR 1016 OR 1254 DID NOT ALTER BRAIN CATECHOLAMINES NOR DELAYED ALTERNATION PERFORMANCE IN LONG EVANS RATS

    EPA Science Inventory

    Several reports have indicated that polychlorinated biphenyls (PCB) altered development of biogenic amine systems in the brain, impaired behavioral performances and disrupted maturation of the thyroid axis. The current study examines whether these developmental effects of PCB ar...

  13. OXIDATIVE DNA DAMAGE FROM POTASSIUM BROMATE EXPOSURE IN LONG-EVANS RATS IS NOT ENHANCED BY A MIXTURE OF DRINKING WATER DISINFECTION BY-PRODUCTS

    EPA Science Inventory

    Public drinking water treated with chemical disinfectants contains a complex mixture of disinfection by-products (DBPs) for which the relative toxicity of the mixtures needs to be characterized to accurately assess risk. Potassium bromate (KBrO3) is a by-product from ozonation of...

  14. BRAIN CHOLINESTERASE INHIBITION PRODUCED BY PROPOXUR AND DEPRESSION OF THE PHOTIC AFTER DISCHARGE OF FLASH EVOKED POTENTIALS IN LONG EVANS RATS.

    EPA Science Inventory

    Propoxur is a widely used N-methyl carbamate pesticide that acts by inhibiting cholinesterases (ChE), which may lead to cholinergic toxicity. Flash evoked potentials (FEPs) are a neurophysiological response following stimulation of the visual system with flashes of light. They ar...

  15. Leucocyte responses to fighting in the adult male bandicoot rat.

    PubMed

    Ghosh, P R; Sahu, A; Maiti, B R

    1983-01-01

    The effect of fighting stress on blood leucocyte count was studied in the adult male bandicoot rat. Exposure to fighting stress for 3 h induced neutrophilia, eosinopenia, lymphopenia and monocytopenia. The changes were more significant in the subordinate rat than in the dominant animal. It is suggested that leucocyte responses to fighting are perhaps mediated by the adrenal gland in these animals.

  16. Comparison of the effects of 17 alpha-methyltestosterone, methandrostenolone, and nandrolone decanoate on the sexual behavior of castrated male rats.

    PubMed

    Clark, A S; Fast, A S

    1996-12-01

    In a series of 3 experiments, adult male Long-Evans rats were castrated and treated with 1 of 3 different anabolic-androgenic steroid (AAS) compounds (17 alpha-methyltestosterone, methandrostenolone, or nandrolone decanoate) for 6 weeks. In each experiment, subjects received daily injections of a high, medium, or low dose of AAS or the oil vehicle. The AAS effects on body weight in gonadectomized male rats were modest, and no effects on locomotor activity were observed. The AAS compounds administered at doses comparable with human abuse levels were not equipotent in maintaining male sexual behavior patterns (nandrolone decanoate > methandrostenolone > 17 alpha-methyltestosterone). In addition, the behavioral actions of AAS compounds did not parallel stimulation of sexual accessory glands. The authors reported that this study is the first to quantify the dose-response characteristics of individual AAS compounds with regard to these behavioral and endocrine measures. PMID:8986348

  17. GESTATIONAL EXPOSURE TO NONYLPHENOL CAUSES PRECOCIOUS MAMMARY GLAND DEVELOPMENT IN FEMALE RAT OFFSPRING

    EPA Science Inventory

    This study examined whether or not exposure to 4-nonylphenol (NP) during late gestation affects reproductive and mammary development in the offspring of female rats. Time pregnant Long Evans rats were gavaged with NP (10 or 100 mg/kg), atrazine (ATR, 100 mg/kg), or corn oil on ge...

  18. A Transgenic Rat for Specifically Inhibiting Adult Neurogenesis123

    PubMed Central

    Grigereit, Laura; Pickel, James

    2016-01-01

    Abstract The growth of research on adult neurogenesis and the development of new models and tools have greatly advanced our understanding of the function of newborn neurons in recent years. However, there are still significant limitations in the ability to identify the functions of adult neurogenesis in available models. Here we report a transgenic rat (TK rat) that expresses herpes simplex virus thymidine kinase in GFAP+ cells. Upon treating TK rats with the antiviral drug valganciclovir, granule cell neurogenesis can be completely inhibited in adulthood, in both the hippocampus and olfactory bulb. Interestingly, neurogenesis in the glomerular and external plexiform layers of the olfactory bulb was only partially inhibited, suggesting that some adult-born neurons in these regions derive from a distinct precursor population that does not express GFAP. Within the hippocampus, blockade of neurogenesis was rapid and nearly complete within 1 week of starting treatment. Preliminary behavioral analyses indicate that general anxiety levels and patterns of exploration are generally unaffected in neurogenesis-deficient rats. However, neurogenesis-deficient TK rats showed reduced sucrose preference, suggesting deficits in reward-related behaviors. We expect that TK rats will facilitate structural, physiological, and behavioral studies that complement those possible in existing models, broadly enhancing understanding of the function of adult neurogenesis. PMID:27257630

  19. Conditioned fear in adult rats is facilitated by the prior acquisition of a classically conditioned motor response

    PubMed Central

    Lindquist, Derick H.; Mahoney, Luke P.; Steinmetz, Joseph E.

    2010-01-01

    Early in eyeblink classical conditioning, amygdala-dependent fear responding is reported to facilitate acquisition of the cerebellar-dependent eyeblink conditioned response (CR), in accord with the two-process model of conditioning (Konorski, 1967). In the current study, we predicted that the conditioned fear (e.g., freezing) observed during eyeblink conditioning may become autonomous of the eyeblink CR and amenable to further associative modification. Conditioned freezing was assessed during and following Pavlovian fear conditioning in Long-Evans rats that had or had not undergone eight prior sessions of eyeblink conditioning. The amplitude and frequency of the tone conditioned stimulus (CS) was held constant across both forms of conditioning. Following fear conditioning in Experiment 1, freezing to the tone CS, but not the context, was facilitated in rats that previously experienced CS-unconditioned stimulus (US) paired eyeblink conditioning. In Experiment 2, freezing immediately following each fear conditioning trial was enhanced in rats subjected to the antecedent eyeblink conditioning, indicating a faster acquisition rate. Finally, in Experiment 3, faster acquisition was seen only in those rats fear conditioned in the same context used for the prior eyeblink conditioning. Taken together, the data indicate that the conditioned fear associated with the context and CS as a result of eyeblink conditioning can be built upon or strengthened during subsequent learning. PMID:20493273

  20. Dendrites and Cognition: A Negative Pilot Study in the Rat.

    ERIC Educational Resources Information Center

    Anderson, Britt

    1995-01-01

    The dendritic structure of layer II-III pyramidal neurons of the parietal cortex in 41 Long-Evans rats was compared to behavioral assessments of attention to novelty, response flexibility, and reasoning. A significant correlation between dendritic arborization and behavioral performance was not demonstrated. (SLD)

  1. EFFECT OF ATRAZINE ON OVARIAN FUNCTION IN THE RAT

    EPA Science Inventory

    The effect of the chlorotriazine herbicide, atrazine, on ovarian function was studied in Long-Evans hooded (LE-hooded) and SpragucDawley (SD) rats. Atrazine was administered by gavage for 21 d to females displaying regular 4-d estrous cycles. In both sfrains, 75 mg/kg/d disrupted...

  2. Comprehensive Assessment of Oxidatively Induced Modifications of DNA in a Rat Model of Human Wilson's Disease.

    PubMed

    Yu, Yang; Guerrero, Candace R; Liu, Shuo; Amato, Nicholas J; Sharma, Yogeshwar; Gupta, Sanjeev; Wang, Yinsheng

    2016-03-01

    Defective copper excretion from hepatocytes in Wilson's disease causes accumulation of copper ions with increased generation of reactive oxygen species via the Fenton-type reaction. Here we developed a nanoflow liquid chromatography-nanoelectrospray ionization-tandem mass spectrometry coupled with the isotope-dilution method for the simultaneous quantification of oxidatively induced DNA modifications. This method enabled measurement, in microgram quantities of DNA, of four oxidative stress-induced lesions, including direct ROS-induced purine cyclonucleosides (cPus) and two exocyclic adducts induced by byproducts of lipid peroxidation, i.e. 1,N(6)-etheno-2'-deoxyadenosine (εdA) and 1,N(2)-etheno-2'-deoxyguanosine (εdG). Analysis of liver tissues of Long-Evans Cinnamon rats, which constitute an animal model of human Wilson's disease, and their healthy counterparts [i.e. Long-Evans Agouti rats] showed significantly higher levels of all four DNA lesions in Long-Evans Cinnamon than Long-Evans Agouti rats. Moreover, cPus were present at much higher levels than εdA and εdG lesions. In contrast, the level of 5-hydroxymethyl-2'-deoxycytidine (5-HmdC), an oxidation product of 5-methyl-2'-deoxycytidine (5-mdC), was markedly lower in the liver tissues of Long-Evans Cinnamon than Long-Evans Agouti rats, though no differences were observed for the levels of 5-mdC. In vitro biochemical assay showed that Cu(2+) ions could directly inhibit the activity of Tet enzymes. Together, these results suggest that aberrant copper accumulation may perturb genomic stability by elevating oxidatively induced DNA lesions, and by altering epigenetic pathways of gene regulation.

  3. Physiological responses during whole body suspension of adult rats

    NASA Technical Reports Server (NTRS)

    Steffen, J. M.; Fell, R. D.; Musacchia, X. J.

    1987-01-01

    The objective of this study was to characterize responses of adult rats to one and two weeks of whole body suspension. Body weights and food and water intakes were initially reduced during suspension, but, while intake of food and water returned to presuspension levels, body weight remained depressed. Diuresis was evident, but only during week two. Hindlimb muscle responses were differential, with the soleus exhibiting the greatest atrophy and the EDL a relative hypertrophy. These findings suggest that adult rats respond qualitatively in a manner similar to juveniles during suspension.

  4. LONG-LASTING NEUROSTRUCTURAL CONSEQUENCES IN THE RAT HIPPOCAMPUS BY DEVELOPMENTAL EXPOSURE TO A MIXTURE OF POLYCHLORINATED BIPHENYLS (PCBS).

    EPA Science Inventory

    The objective of the study was to assess the effects of developmental exposure to a commercial mixture of PCBs (Aroclor 1254) on neuronal dendritic morphology of hippocampal CA1 pyramidal neurons in postnatal day (PND) 22 and PND 60 male Long-Evans rats. Rat pups were born to mot...

  5. Acute prenatal exposure to ethanol on gestational day 12 elicits opposing deficits in social behaviors and anxiety-like behaviors in Sprague Dawley rats.

    PubMed

    Diaz, Marvin R; Mooney, Sandra M; Varlinskaya, Elena I

    2016-09-01

    Our previous research has shown that in Long Evans rats acute prenatal exposure to a high dose of ethanol on gestational day (G) 12 produces social deficits in male offspring and elicits substantial decreases in social preference relative to controls, in late adolescents and adults regardless of sex. In order to generalize the observed detrimental effects of ethanol exposure on G12, pregnant female Sprague Dawley rats were exposed to ethanol or saline and their offspring were assessed in a modified social interaction (SI) test as early adolescents, late adolescents, or young adults. Anxiety-like behavior was also assessed in adults using the elevated plus maze (EPM) or the light/dark box (LDB) test. Age- and sex-dependent social alterations were evident in ethanol-exposed animals. Ethanol-exposed males showed deficits in social investigation at all ages and age-dependent alterations in social preference. Play fighting was not affected in males. In contrast, ethanol-exposed early adolescent females showed no changes in social interactions, whereas older females demonstrated social deficits and social indifference. In adulthood, anxiety-like behavior was decreased in males and females prenatally exposed to ethanol in the EPM, but not the LDB. These findings suggest that social alterations associated with acute exposure to ethanol on G12 are not strain-specific, although they are more pronounced in Long Evans males and Sprague Dawley females. Furthermore, given that anxiety-like behaviors were attenuated in a test-specific manner, this study indicates that early ethanol exposure can have differential effects on different forms of anxiety. PMID:27154534

  6. Leptin inhibits testosterone secretion from adult rat testis in vitro.

    PubMed

    Tena-Sempere, M; Pinilla, L; González, L C; Diéguez, C; Casanueva, F F; Aguilar, E

    1999-05-01

    Leptin, the product of the ob gene, has emerged recently as a pivotal signal in the regulation of fertility. Although the actions of leptin in the control of reproductive function are thought to be exerted mainly at the hypothalamic level, the potential direct effects of leptin at the pituitary and gonadal level have been poorly characterised. In the present study, we first assessed the ability of leptin to regulate testicular testosterone secretion in vitro. Secondly, we aimed to evaluate whether leptin can modulate basal gonadotrophin and prolactin (PRL) release by incubated hemi-pituitaries from fasted male rats. To attain the first goal, testicular slices from prepubertal and adult rats were incubated with increasing concentrations (10(-9)-10(-7) M) of recombinant leptin. Assuming that in vitro testicular responsiveness to leptin may be dependent on the background leptin levels, testicular tissue from both food-deprived and normally-fed animals was used. Furthermore, leptin modulation of stimulated testosterone secretion was evaluated by incubation of testicular samples with different doses of leptin in the presence of 10 IU human chorionic gonadotrophin (hCG). In addition, analysis of leptin actions on pituitary function was carried out using hemi-pituitaries from fasted adult male rats incubated in the presence of increasing concentrations (10(-9)-10(-7) M) of recombinant leptin. Serum testosterone levels, and basal and hCG-stimulated testosterone secretion by incubated testicular tissue were significantly decreased by fasting in prepubertal and adult male rats. However, a significant reduction in circulating LH levels was only evident in adult fasted rats. Doses of 10(-9)-10(-7) M leptin had no effect on basal or hCG-stimulated testosterone secretion by testes from prepubertal rats, regardless of the nutritional state of the donor animal. In contrast, leptin significantly decreased basal and hCG-induced testosterone secretion by testes from fasted and fed

  7. Leptin inhibits testosterone secretion from adult rat testis in vitro.

    PubMed

    Tena-Sempere, M; Pinilla, L; González, L C; Diéguez, C; Casanueva, F F; Aguilar, E

    1999-05-01

    Leptin, the product of the ob gene, has emerged recently as a pivotal signal in the regulation of fertility. Although the actions of leptin in the control of reproductive function are thought to be exerted mainly at the hypothalamic level, the potential direct effects of leptin at the pituitary and gonadal level have been poorly characterised. In the present study, we first assessed the ability of leptin to regulate testicular testosterone secretion in vitro. Secondly, we aimed to evaluate whether leptin can modulate basal gonadotrophin and prolactin (PRL) release by incubated hemi-pituitaries from fasted male rats. To attain the first goal, testicular slices from prepubertal and adult rats were incubated with increasing concentrations (10(-9)-10(-7) M) of recombinant leptin. Assuming that in vitro testicular responsiveness to leptin may be dependent on the background leptin levels, testicular tissue from both food-deprived and normally-fed animals was used. Furthermore, leptin modulation of stimulated testosterone secretion was evaluated by incubation of testicular samples with different doses of leptin in the presence of 10 IU human chorionic gonadotrophin (hCG). In addition, analysis of leptin actions on pituitary function was carried out using hemi-pituitaries from fasted adult male rats incubated in the presence of increasing concentrations (10(-9)-10(-7) M) of recombinant leptin. Serum testosterone levels, and basal and hCG-stimulated testosterone secretion by incubated testicular tissue were significantly decreased by fasting in prepubertal and adult male rats. However, a significant reduction in circulating LH levels was only evident in adult fasted rats. Doses of 10(-9)-10(-7) M leptin had no effect on basal or hCG-stimulated testosterone secretion by testes from prepubertal rats, regardless of the nutritional state of the donor animal. In contrast, leptin significantly decreased basal and hCG-induced testosterone secretion by testes from fasted and fed

  8. Strain and sex differences in brain and behaviour of adult rats: Learning and memory, anxiety and volumetric estimates.

    PubMed

    Keeley, R J; Bye, C; Trow, J; McDonald, R J

    2015-07-15

    Alterations in behaviour can arise through a number of factors, including strain and sex. Here, we explored strain and sex differences between Long-Evans (LER) and Wistar (WR) male and female rats that had been trained in a myriad of behavioural tasks. Tests included those assessing motor learning (skilled reaching task), spatial learning and memory (Morris water task), contextual learning (discriminative fear-conditioning to context) and anxiety behaviour (elevated plus maze). Following behavioural assessment, associated brain areas were examined for volumetric differences, including the hippocampus and its subregions, prefrontal cortex areas and the amygdala. LER and WR differed in their rates of performance in the skilled reaching task throughout the training period. Overall, LER outperformed WR in tasks related to contextual and spatial learning, although this was not accompanied by larger volumes of associated brain areas. Males outperformed females in spatial learning, and females outperformed males in the contextual fear-conditioning task and had an associated larger amygdalar volume, although these sexual dimorphisms were only observed within the LER strain. Overall, this study highlights differences between these two rat strains as well as highlights that larger volumetric estimates of brain areas do not always confer improved function of associated behaviours.

  9. STRAIN COMPARISONS OF ATRAZINE-INDUCED PREGNANCY LOSS IN THE RAT

    EPA Science Inventory

    Atrazine was administered by gavage, in 1% methylcellulose, to F344, Sprague-Dawley (SD), and Long Evans (LE) rats at 0, 25, 50, 100, or 200 mg/kg/d on gestation days 6-10. The dams were allowed to deliver and litters were examined postnatally. The F344 strain was the most sens...

  10. GESTATIONAL MERCURY VAPOR EXPOSURE AND DIET CONTRIBUTE TO MERCURY ACCUMULATION IN NEONATAL RATS.

    EPA Science Inventory

    Exposure of pregnant Long-Evans rats to elemental mercury (Hg0) vapor resulted in a significant

    accumulation of Hg in tissues of neonates. Because elevated Hg in neonatal tissues may adversely

    affect growth and development, we were interested in how rapidly Hg was...

  11. Age-related changes in body composition in laboratory rats: Strain and gender comparisons

    EPA Science Inventory

    Long Evans (LE), Sprague Dawley (SD), Fischer 344 (F344), and Brown Norway (BN) rats are all commonly used as laboratory research subjects. These strains have been studied under many conditions, but few studies have measured changes in body composition as the animals age. Underst...

  12. Reproductive toxicity of DDT in adult male rats.

    PubMed

    Ben Rhouma, K; Tébourbi, O; Krichah, R; Sakly, M

    2001-08-01

    The reproductive toxicity of DDT was investigated in adult male rats exposed to 50 and 100 mg/kg body weight (b.wt) day(-1) for 10 successive days. Compared with control animals, administration of DDT led to a dose-dependent reduction of testicular weight and the number as well as the percentage of motile spermatozoa in the epididymis. Testicular histological observations revealed also a marked loss of gametes in the lumen of seminiferous tubules. In DDT-treated rats, the seminal vesicles weights dropped significantly, resulting from a decrease of testosterone production by testes, whereas serum LH and FSH increased after pesticide exposure. This increase of gonadotrophin levels may be related to an impairment of the negative feedback exerted by the steroid on the hypothalamic--pituitary axis. It is concluded that DDT induced adverse effects on male rat fertility by acting directly on the testes and altering the neuroendocrine function.

  13. Toxicity of zinc oxide nanoparticles on adult male Wistar rats.

    PubMed

    Abbasalipourkabir, Roghayeh; Moradi, Hemen; Zarei, Sadegh; Asadi, Soheila; Salehzadeh, Aref; Ghafourikhosroshahi, Abolfazl; Mortazavi, Motahareh; Ziamajidi, Nasrin

    2015-10-01

    The purpose of this study was to investigate the effects of zinc oxide nanoparticles (nZnO) on adult male Wistar rats. Thirty male Wistar rats divided into five groups of six animals each were used for this study. For ten days, Groups one to four continuously received 50, 100, 150 and 200 mg/kg nZnO, respectively. Group five served as the control group. At the end of the study, the rats were sacrificed and histopathological study of the liver and renal tissue, sperm analysis, serum oxidative stress parameters and some liver enzymes were done. The results of this study showed that nZnO at concentration more than 50 mg/kg lead to significant changes in liver enzymes, oxidative stress, liver and renal tissue and sperm quality and quantity. In conclusion, the toxicity of nZnO is more significant when the concentration is increased; however, the use of low doses requires further investigation.

  14. Ketone-body utilization by homogenates of adult rat brain

    SciTech Connect

    Lopes-Cardozo, M.; Klein, W.

    1982-06-01

    The regulation of ketone-body metabolism and the quantitative importance of ketone bodies as lipid precursors in adult rat brain has been studied in vitro. Utilization of ketone bodies and of pyruvate by homogenates of adult rat brain was measured and the distribution of /sup 14/C from (3-/sup 14/C)ketone bodies among the metabolic products was analysed. The rate of ketone-body utilization was maximal in the presence of added Krebs-cycle intermediates and uncouplers of oxidative phosphorylation. The consumption of acetoacetate was faster than that of D-3-hydroxybutyrate, whereas, pyruvate produced twice as much acetyl-CoA as acetoacetate under optimal conditions. Millimolar concentrations of ATP in the presence of uncoupler lowered the consumption of ketone bodies but not of pyruvate. Indirect evidence is presented suggesting that ATP interferes specifically with the mitochondrial uptake of ketone bodies. Interconversion of ketone bodies and the accumulation of acid-soluble intermediates (mainly citrate and glutamate) accounted for the major part of ketone-body utilization, whereas only a small part was oxidized to CO/sub 2/. Ketone bodies were not incorporated into lipids or protein. We conclude that adult rat-brain homogenates use ketone bodies exclusively for oxidative purposes.

  15. Contextual fear conditioning differs for infant, adolescent, and adult rats.

    PubMed

    Esmorís-Arranz, Francisco J; Méndez, Cástor; Spear, Norman E

    2008-07-01

    Contextual fear conditioning was tested in infant, adolescent, and adult rats in terms of Pavlovian-conditioned suppression. When a discrete auditory-conditioned stimulus (CS) was paired with footshock (unconditioned stimulus, US) within the largely olfactory context, infants and adolescents conditioned to the context with substantial effectiveness, but adult rats did not. When unpaired presentations of the CS and US occurred within the context, contextual fear conditioning was strong for adults, weak for infants, but about as strong for adolescents as when pairings of CS and US occurred in the context. Nonreinforced presentations of either the CS or context markedly reduced contextual fear conditioning in infants, but, in adolescents, CS extinction had no effect on contextual fear conditioning, although context extinction significantly reduced it. Neither CS extinction nor context extinction affected responding to the CS-context compound in infants, suggesting striking discrimination between the compound and its components. Female adolescents showed the same lack of effect of component extinction on response to the compound as infants, but CS extinction reduced responding to the compound in adolescent males, a sex difference seen also in adults. Theoretical implications are discussed for the development of perceptual-cognitive processing and hippocampus role.

  16. Intestinal absorption of aspartame decomposition products in adult rats.

    PubMed

    Lipton, W E; Li, Y N; Younoszai, M K; Stegink, L D

    1991-12-01

    The dipeptide sweetener aspartame (N-L-alpha-aspartyl-L-phenylalanine, 1-methyl ester; alpha-APM) is relatively stable in dry powder form. However, when exposed to elevated temperature, extremes of pH and/or moisture, alpha-APM is converted into a variety of products. In aqueous solution alpha-APM decomposes to yield methanol, two isomeric forms of L-aspartyl-L-phenylalanine (Asp-Phe) [alpha-Asp-Phe and beta-Asp-Phe], and APM's diketopiperazine cyclo-Asp-Phe. Depending on beverage storage conditions, individuals drinking alpha-APM-sweetened beverages may consume small quantities of these three compounds. Relatively little has been published about the metabolism of beta-Asp-Phe and cyclo-Asp-Phe. We compared the absorption and metabolism of alpha-Asp-Phe, beta-Asp-Phe, and cyclo-Asp-Phe with that of L-phenylalanine (Phe) in adult rats. Steady-state perfusion studies of rat jejunum indicated rapid carrier-assisted uptake of Phe and alpha-Asp-Phe, but only slow passive diffusion of beta-Asp-Phe and cyclo-Asp-Phe from the lumen. Homogenates of rat intestinal mucosa, liver, and cecal contents, as well as homogenates of pure cultures of Escherichia coli B, catalyzed the hydrolysis of alpha-Asp-Phe, but not cyclo-Asp-Phe. Homogenates of E coli and rat cecal contents, but not homogenates of rat liver or intestinal mucosa catalyzed the hydrolysis of beta-Asp-Phe.

  17. Plexin a4 expression in adult rat cranial nerves.

    PubMed

    Gutekunst, Claire-Anne; Gross, Robert E

    2014-11-01

    PlexinsA1-A4 participate in class 3 semaphorin signaling as co-receptors to neuropilin 1 and 2. PlexinA4 is the latest member of the PlexinA subfamily to be identified. In previous studies, we described the expression of PlexinA4 in the brain and spinal cord of the adult rat. Here, antibodies to PlexinA4 were used to reveal immunolabeling in most of the cranial nerve surveyed. Labeling was found in the olfactory, optic, oculomotor, trochlear, trigeminal, abducens, facial, vestibulocochlear, glossopharyngeal, vagus, and hypoglossal nerves. This is the first detailed description of the cellular and subcellular distribution of PlexinA4 in the adult cranial nerves. The findings will set the basis for future studies on the potential role of PlexinA4 in regeneration and repair of the adult central and peripheral nervous system.

  18. Obesity-related changes in bone structural and material properties in hyperphagic OLETF rats and protection by voluntary wheel running

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We conducted a study to examine how the development of obesity and the associated insulin resistance affect bone structural and material properties, and bone formation and resorption markers in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat model. This was a 36-week study of sedentary, hyperphag...

  19. Prenatal Ethanol Exposure Increases Brain Cholesterol Content in Adult Rats

    PubMed Central

    Barceló-Coblijn, Gwendolyn; Wold, Loren E.; Ren, Jun; Murphy, Eric J.

    2013-01-01

    Fetal alcohol syndrome is the most severe expression of the fetal alcohol spectrum disorders (FASD). Although alterations in fetal and neonate brain fatty acid composition and cholesterol content is known to change in animal models of FASD, the persistence of these alterations into adulthood is unknown. To address this question, we determined the effect of prenatal ethanol exposure on individual phospholipid class fatty acid composition, individual phospholipid class mass, and cholesterol mass in brains from 25-week-old rats that were exposed to ethanol during gestation beginning at gestational day 2. While total phospholipid mass was unaffected, phosphatidylinositol and cardiolipin mass was decreased 14 and 43%, respectively. Exposure to prenatal ethanol modestly altered brain phospholipid fatty acid composition, and the most consistent change was a significant 1.1-fold increase in total PUFA, in the n-3/n-6 ratio, and in the 22:6 n-3 content in ethanolamine glycerophospholipids and in phosphatidylserine. In contrast, prenatal ethanol consumption significantly increased brain cholesterol mass 1.4-fold and the phospholipid to cholesterol ratio was significantly increased 1.3-fold. These results indicate that brain cholesterol mass was significantly increased in adult rats exposed prenatally to ethanol, but changes in phospholipid mass and phospholipid fatty acid composition were extremely limited. Importantly, suppression of post-natal ethanol consumption was not sufficient to reverse the large increase in cholesterol observed in the adult rats. PMID:23996454

  20. Selective cognitive deficits in adult rats after prenatal exposure to inhaled ethanol.

    PubMed

    Oshiro, W M; Beasley, T E; McDaniel, K L; Taylor, M M; Evansky, P; Moser, V C; Gilbert, M E; Bushnell, P J

    2014-01-01

    Increased use of ethanol blends in gasoline suggests a need to assess the potential public health risks of exposure to these fuels. Ethanol consumed during pregnancy is a teratogen. However, little is known about the potential developmental neurotoxicity of ethanol delivered by inhalation, the most likely route of exposure from gasoline-ethanol fuel blends. We evaluated the potential cognitive consequences of ethanol inhalation by exposing pregnant Long Evans rats to clean air or ethanol vapor from gestational days 9-20, a critical period of neuronal development. Concentrations of inhaled ethanol (5000, 10,000, or 21,000 ppm for 6.5h/day) produced modeled peak blood ethanol concentrations (BECs) in exposed dams of 2.3, 6.8, and 192 mg/dL, respectively. In offspring, no dose-related impairments were observed on spatial learning or working memory in the Morris water maze or in operant delayed match-to-position tests. Two measures showed significant effects in female offspring at all ethanol doses: 1) impaired cue learning after trace fear conditioning, and 2) an absence of bias for the correct quadrant after place training during a reference memory probe in the Morris water maze. In choice reaction time tests, male offspring (females were not tested) from the 5000 and 10,000 ppm groups showed a transient increase in decision times. Also, male offspring from the 21,000 ppm group made more anticipatory responses during a preparatory hold period, suggesting a deficit in response inhibition. The increase in anticipatory responding during the choice reaction time test shows that inhaled ethanol yielding a peak BEC of ~200mg/dL can produce lasting effects in the offspring. The lack of a dose-related decrement in the effects observed in females on cue learning and a reference memory probe may reflect confounding influences in the exposed offspring possibly related to maternal care or altered anxiety levels in females. The surprising lack of more pervasive cognitive deficits

  1. Respiratory tract lung geometry and dosimetry model for male Sprague-Dawley rats.

    SciTech Connect

    Miller, Frederick J.; Asgharian, Bahman; Schroeter, Jeffry D.; Price, Owen; Corley, Richard A.; Einstein, Daniel R.; Jacob, Rick E.; Cox, Timothy C.; Kabilan, Senthil; Bentley, Timothy

    2014-08-26

    While inhalation toxicological studies of various compounds have been conducted using a number of different strains of rats, mechanistic dosimetry models have only had tracheobronchial (TB) structural data for Long-Evans rats, detailed morphometric data on the alveolar region of Sprague-Dawley rats and limited alveolar data on other strains. Based upon CT imaging data for two male Sprague-Dawley rats, a 15-generation, symmetric typical path model was developed for the TB region. Literature data for the alveolar region of Sprague-Dawley rats were analyzed to develop an eight-generation model, and the two regions were joined to provide a complete lower respiratory tract model for Sprague-Dawley rats. The resulting lung model was used to examine particle deposition in Sprague-Dawley rats and to compare these results with predicted deposition in Long-Evans rats. Relationships of various physiologic variables and lung volumes were either developed in this study or extracted from the literature to provide the necessary input data for examining particle deposition. While the lengths, diameters and branching angles of the TB airways differed between the two Sprague- Dawley rats, the predicted deposition patterns in the three major respiratory tract regions were very similar. Between Sprague-Dawley and Long-Evans rats, significant differences in TB and alveolar predicted deposition fractions were observed over a wide range of particle sizes, with TB deposition fractions being up to 3- to 4-fold greater in Sprague-Dawley rats and alveolar deposition being significantly greater in Long-Evans rats. Thus, strain-specific lung geometry models should be used for particle deposition calculations and interspecies dose comparisons.

  2. Respiratory Tract Lung Geometry and Dosimetry Model for Male Sprague-Dawley Rats

    SciTech Connect

    Miller, Frederick J.; Asgharian, Bahman; Schroeter, Jeffry D.; Price, Owen; Corley, Richard A.; Einstein, Daniel R.; Jacob, Rick E.; Cox, Timothy C.; Kabilan, Senthil; Bentley, Timothy

    2015-07-24

    While inhalation toxicological studies of various compounds have been conducted using a number of different strains of rats, mechanistic dosimetry models have only had tracheobronchial (TB) structural data for Long-Evans rats, detailed morphometric data on the alveolar region of Sprague-Dawley rats and limited alveolar data on other strains. Based upon CT imaging data for two male Sprague-Dawley rats, a 15-generation, symmetric typical path model was developed for the TB region. Literature data for the alveolar region of Sprague-Dawley rats were analyzed to develop an eight-generation model, and the two regions were joined to provide a complete lower respiratory tract model for Sprague-Dawley rats. The resulting lung model was used to examine particle deposition in Sprague-Dawley rats and to compare these results with predicted deposition in Long-Evans rats. Relationships of various physiologic variables and lung volumes were either developed in this study or extracted from the literature to provide the necessary input data for examining particle deposition. While the lengths, diameters and branching angles of the TB airways differed between the two Sprague-Dawley rats, the predicted deposition patterns in the three major respiratory tract regions were very similar. Between Sprague-Dawley and Long-Evans rats, significant differences in TB and alveolar predicted deposition fractions were observed over a wide range of particle sizes, with TB deposition fractions being up to 3- to 4-fold greater in Sprague-Dawley rats and alveolar deposition being significantly greater in Long-Evans rats. Thus, strain-specific lung geometry models should be used for particle deposition calculations and interspecies dose comparisons.

  3. Effects of Adolescent Ethanol Exposure on Sleep in Adults Rats

    PubMed Central

    Criado, José R.; Wills, Derek N.; Walker, Brendan M.; Ehlers, Cindy L.

    2010-01-01

    Although adolescent ethanol (EtOH) exposure has been associated with long-lasting changes in brain function, little is known as to whether EtOH exposure during adolescence alters sleep and cortical arousal. This study examined protracted alterations in sleep in adult rats exposed to EtOH during adolescence. Adolescent male Wistar rats were exposed to EtOH vapor for 12 hr/day for five weeks. Cortical electroencephalograms (EEGs) were obtained during 4-hr recording sessions after five weeks of withdrawal from EtOH. Adolescent EtOH exposure significantly reduced the mean duration of slow-wave sleep (SWS) episodes and the total amount of time spent in SWS in EtOH-exposed rats, compared to controls. Spectral analysis revealed that adolescent EtOH exposure significantly increased cortical peak frequencies during SWS in the 2-4 Hz, 4-6 Hz and 6-8 Hz bands. Taken together, our findings suggest that chronic EtOH exposure in adolescent rats reduces measures of SWS, an effect also seen as part of normal aging. Although the cellular and molecular mechanisms mediating the consequences of EtOH exposure on the aging process are not known, the similarities between adolescent EtOH exposure and aging merits further investigation. PMID:18922666

  4. Preproglucagon mRNA expression in adult rat submandibular glands.

    PubMed

    Egéa, J C; Hirtz, C; Deville de Périère, D

    2003-04-01

    Salivary glands of various animal species have been reported to contain and suggested to produce glucagon or glucagon-like material, but the origin and the nature of this salivary peptide are still doubtful. The present study was undertaken to ascertain whether the glucagon gene is expressed in rat submandibular glands and in an immortalized murine cell line derived from salivary glands (SCA-9 cell line). For this purpose, total RNA was isolated from submandibular glands or cultured cells and submitted to reverse transcription. The cDNAs obtained were amplified by a nested polymerase chain reaction using preproglucagon primers. The results showed that the preproglucagon mRNA was expressed in adult rat submandibular glands but not in the SCA-9 cell line. Determination of cyclic DNA (cDNA) sequence established identity with the coding regions of rat pancreatic pre-proglucagon gene. In conclusion, these results strongly support the idea that rat submandibular glands could represent a source of extrapancreatic glucagon or of its precursor's peptide.

  5. Maternal hyperthyroidism in rats impairs stress coping of adult offspring.

    PubMed

    Zhang, Limei; Hernández, Vito S; Medina-Pizarro, Mauricio; Valle-Leija, Pablo; Vega-González, Arturo; Morales, Teresa

    2008-05-01

    Given the evidence that maternal hyperthyroidism (MH) compromises expression of neuronal cytoskeletal proteins in the late fetal brain by accelerated neuronal differentiation, we investigated possible consequences of MH for the emotional and cognitive functions of adult offspring during acute and subchronic stress coping. Experimental groups consisted of male rat offspring from mothers implanted with osmotic minipumps infusing either thyroxine (MH) or vehicle (Ctrl) during pregnancy. Body weight and T4 level were monitored during the first 3 postnatal months, and no differences were found with the controls. We analyzed hippocampal CA3 pyramidal neurons and dentate granular cell morphology during several postnatal stages and found increased dendritic arborization. On postnatal day 90 a modified subchronic mild stress (SCMS) protocol was applied to experimental subjects for 10 days. The Morris water maze was used before, during, and after application of the SCMS protocol to measure spatial learning. The tail suspension test (TST) and forced-swimming test (FST) were used to evaluate behavioral despair. The MH rats displayed normal locomotor activity and spatial memory prior to SCMS, but impaired spatial learning after acute and chronic stress. In both the FST and TST we found that MH rats spent significantly more time immobile than did controls. Serum corticosterone level was found to increase after 30 min of restraint stress, and corticotropin-releasing factor immunoreactivity was found to be increased in the central nucleus of the amygdala. Our results suggest that MH in rats leads to the offspring being more vulnerable to stress in adulthood.

  6. [Average values of electrocardiograph parameters in healthy, adult Wistar rats].

    PubMed

    Zaciragić, Asija; Nakas-ićindić, Emina; Hadzović, Almira; Avdagić, Nesina

    2004-01-01

    Average values of heart rate (HR) and the average duration of electrocardiograph parameters were investigated (RR interval, P wave, PQ interval, QRS complex and QT interval) in healthy, adult Wistar rats of both sexes (n=86). Electrocardiogram (ECG) was recorded by Shiller Resting ECG, and for analysis of recordings SEMA-200 Vet computer program was used. Prior to registration animals were exposed to light ether anesthesia. Mean value of HR was 203.03+/-3.09 beats/min in whole sample. Observed differences in mean values of heart rate and duration of followed ECG parameters between sexes were not statistically significant. Results gathered in our study could serve as standard values for electrocardiograph parameters in future research where will be used Wistar rats in conditions of registration and analysis of ECG that are described in our paper.

  7. Social instability stress in adolescent male rats alters hippocampal neurogenesis and produces deficits in spatial location memory in adulthood.

    PubMed

    McCormick, Cheryl M; Thomas, Catherine M; Sheridan, Cheryl S; Nixon, Feather; Flynn, Jennifer A; Mathews, Iva Z

    2012-06-01

    The ongoing development of the hippocampus in adolescence may be vulnerable to stressors. The effects of social instability stress (SS) in adolescence (daily 1 h isolation and change of cage partner postnatal days 30-45) on cell proliferation in the dentate gyrus (DG) in adolescence (on days 33 and 46, experiment 1) and in adulthood (experiment 2) was examined in Long Evans male rats and compared to nonstressed controls (CTL). Additionally, in experiment 2, a separate group of SS and CTL rats was tested on either a spatial (hippocampal-dependent) or nonspatial (nonhippocampal dependent) version of an object memory test and also were used to investigate hippocampal expression of markers of synaptic plasticity. No memory impairment was evident until the SS rats were adults, and the impairment was only on the spatial test. SS rats initially (postnatal day 33) had increased cell proliferation based on counts of Ki67 immunoreactive (ir) cells and greater survival of immature neurons based on counts of doublecortin ir cells on day 46 and in adulthood, irrespective of behavioral testing. Counts of microglia in the DG did not differ by stress group, but behavioral testing was associated with reduced microglia counts compared to nontested rats. As adults, SS and CTL rats did not differ in hippocampal expression of synaptophysin, but compared to CTL rats, SS rats had higher expression of basal calcium/calmodulin-dependent kinase II (CamKII), and lower expression of the phosphorylated CamKII subunit threonine 286, signaling molecules related to synaptic plasticity. The results are contrasted with those from previous reports of chronic stress in adult rats, and we conclude that adolescent stress alters the ongoing development of the hippocampus leading to impaired spatial memory in adulthood, highlighting the heightened vulnerability to stressors in adolescence.

  8. Impaired spatial performance in rats with retrosplenial lesions: importance of the spatial problem and the rat strain in identifying lesion effects in a swimming pool.

    PubMed

    Harker, K Troy; Whishaw, Ian Q

    2002-02-01

    Behavioral, electrophysiological, and anatomical evidence suggests that retrosplenial (RS) cortex (areas RSA and RSG) plays a role in spatial navigation. This conclusion has been questioned in recent work, suggesting that it is damage to the underlying cingulum bundle (CG) (areas CG and IG), and not RS, that disrupts spatial place learning (Aggleton et al., 2000). We revisited this issue by comparing Long-Evans rats, the strain used in studies that report RS deficits, to Dark Agouti rats, the strain in which no RS deficit has been reported. Rat groups with RS, RS + CG, or no lesion were tested on a place task in a swimming pool, a test of nonspatial and spatial learning, and a matching-to-place task, a relatively selective test of spatial learning. Long-Evans rats given RS and RS + CG lesions, either before or after training on the two tasks, were impaired on both tasks, a deficit not attributable to impaired visual acuity. Control Dark Agouti rats and RS Dark Agouti rats, although not different on the place task, were both significantly impaired relative to Long-Evans rats. The RS Dark Agouti group, however, was also impaired on the matching-to-place task. Thus, we show that RS cortex is part of an extended neural circuit involved in spatial behavior in both Long-Evans and Dark Agouti rats, but its role in the place task may be masked by an innate nonspatial deficit in Dark Agouti rats. The results are discussed in relation to the importance of assessing spatial learning with appropriate spatial tests, the problems of interpretation posed by rat strain differences, and the role of retrosplenial cortex in spatial behavior.

  9. Mechanically induced orientation of adult rat cardiac myocytes in vitro

    NASA Technical Reports Server (NTRS)

    Samuel, J.-L.; Vandenburgh, H. H.

    1990-01-01

    The present study describes the spatial orientation of a population of freshly isolated adult rat cardiac myocytes using a computerized mechanical cell stimulator device for tissue cultured cells. A continuous unidirectional stretch of the substratum at 60 to 400 microns/min for 120 to 30 min, respectively, during the cell attachment period in a serum-free medium was found to induce a significant threefold increase in the number of rod-shaped myocytes oriented parallel to the direction of movement. The myocytes orient less well with unidirectional substratum stretching after their adhesion to the substratum. Adult myocytes plated onto a substratum undergoing continuous 10-percent stretch-relaxation cycling show no significant change in the myocyte orientation or cytoskeletal organization. In addition to the type of mechanical activity, orientation of rod-shaped myocytes is dependent on the speed of the substratum, the final stretch amplitude, and the timing between initiation of substratum stretching and adhesion of myocytes to the substratum.

  10. Alcohol exposure in utero perturbs retinoid homeostasis in adult rats

    PubMed Central

    Kim, Youn-Kyung; Zuccaro, Michael V.; Zhang, Changqing; Sarkar, Dipak

    2015-01-01

    Background Maternal alcohol exposure and adult alcohol intake have been shown to perturb the metabolism of various micro- and macro-nutrients, including vitamin A and its derivatives (retinoids). Therefore, it has been hypothesized that the well-known detrimental consequences of alcohol consumption may be due to deregulations of the metabolism of such nutrients rather than to a direct effect of alcohol. Alcohol exposure in utero also has long-term harmful consequences on the health of the offspring with mechanisms that have not been fully clarified. Disruption of tissue retinoid homeostasis has been linked not only to abnormal embryonic development, but also to various adult pathological conditions, including cancer, metabolic disorders and abnormal lung function. We hypothesized that prenatal alcohol exposure may permanently perturb tissue retinoid metabolism, predisposing the offspring to adult chronic diseases. Methods Serum and tissues (liver, lung and prostate from males; liver and lung from females) were collected from 60-75 day-old sprague dawley rats born from dams that were: (I) fed a liquid diet containing 6.7% alcohol between gestational day 7 and 21; or (II) pair-fed with isocaloric liquid diet during the same gestational window; or (III) fed ad libitum with regular rat chow diet throughout pregnancy. Serum and tissue retinoid levels were analyzed by reverse-phase high-performance liquid chromatography (HPLC). Serum retinol-binding protein (RBP) levels were measured by western blot analysis, and liver, lung and prostate mRNA levels of lecithin-retinol acyltransferase (LRAT) were measured by qPCR. Results Retinyl ester levels were significantly reduced in the lung of both males and females, as well as in the liver and ventral prostate of males born from alcohol-fed dams. Tissue LRAT mRNA levels remained unchanged upon maternal alcohol treatment. Conclusions Prenatal alcohol exposure in rats affects retinoid metabolism in adult life, in a tissue- and sex

  11. Behavioral effects of repeated handling differ in rats reared in social isolation and environmental enrichment.

    PubMed

    Pritchard, L M; Van Kempen, T A; Zimmerberg, B

    2013-03-01

    The post-weaning social environment has profound effects on behavior and physiology in rodents. Social isolation increases anxiety-like behaviors and novelty-induced locomotor activity, while environmental enrichment decreases these behaviors. In some cases, the effects of social isolation are ameliorated by repeated handling. The goal of the present study was to determine whether the effects of handling differ in rats reared in social isolation and those reared in an enriched environment. After weaning, male Long-Evans rats were housed individually (ISO)(3) or in groups in an enriched environment (EE). During adulthood, rats from each housing condition received four, once-daily, brief handling sessions or remained undisturbed in the home cage. All rats were then tested in the open field, elevated plus maze, and for behavioral responses to d-amphetamine (1.0mg/kg). EE rats spent more time on the open arms of the elevated plus maze and were more likely than ISO rats to emerge from the start box in the open field, suggesting lower anxiety. Handling significantly decreased open arm time in EE rats and marginally increased open arm time in ISO rats. Housing condition did not affect amphetamine-stimulated locomotor activity, but handling altered the time course of the amphetamine response. ISO rats exhibited significantly fewer stereotyped behaviors than did EE rats, but repeated handling eliminated this difference. These findings support previously published studies that suggest brief handling of adult rats may at least partially ameliorate the effects of post-weaning social isolation on anxiety-like behaviors and psychostimulant sensitivity. Furthermore, there are complex interactions between the effects of housing environment and handling, suggesting that handling may be perceived and/or processed differently, depending on the animal's housing environment.

  12. Intermittent exposure of rats to 2450-MHz microwaves at 2. 5 MW cm sq: behavioral and physiological effects

    SciTech Connect

    D'Andrea, J.A.; DeWitt, J.R.; Emmerson, R.Y.; Bailey, C.; Stensaas, S.

    1986-01-01

    Long-Evans male adult rats were intermittently exposed for 14 weeks to continuous wave (c-w) 2450-MHz microwaves at an average power density of 2.5 mW/sq. cm. The mean specific absorption rate was 0.70 W/kg (plus or minus 0.02 SEM). The rats were exposed 7 h/day, 7 days/week in a radiation chamber with a monopole above ground, while housed in Plexiglas cages. Weekly measures of body mass and food intake did not indicate statistically significant effects of microwave irradiation. Assessments of threshold for electric-footshock detection revealed a significant difference between microwave and sham-exposed animals. Assessments of cholinesterase and sulfhydryl groups in blood and 17-ketosteriods, in urine did not distinguish the two groups of rats. Behavioral measures made at the end of the 14-week exposure included an open-field test, shuttlebox avoidance performance, and schedule-controlled lever-pressing for food pellets: Statistically significant differences between microwave- and sham-exposed rats were observed for these measures. Examination of adrenal tissue, plasma electrolytes, and organ masses after 14 weeks of exposure revealed no difference between the two group of rats.

  13. Myogenic regulatory factors during regeneration of skeletal muscle in young, adult, and old rats

    NASA Technical Reports Server (NTRS)

    Marsh, D. R.; Criswell, D. S.; Carson, J. A.; Booth, F. W.

    1997-01-01

    Myogenic factor mRNA expression was examined during muscle regeneration after bupivacaine injection in Fischer 344/Brown Norway F1 rats aged 3, 18, and 31 mo of age (young, adult, and old, respectively). Mass of the tibialis anterior muscle in the young rats had recovered to control values by 21 days postbupivacaine injection but in adult and old rats remained 40% less than that of contralateral controls at 21 and 28 days of recovery. During muscle regeneration, myogenin mRNA was significantly increased in muscles of young, adult, and old rats 5 days after bupivacaine injection. Subsequently, myogenin mRNA levels in young rat muscle decreased to postinjection control values by day 21 but did not return to control values in 28-day regenerating muscles of adult and old rats. The expression of MyoD mRNA was also increased in muscles at day 5 of regeneration in young, adult, and old rats, decreased to control levels by day 14 in young and adult rats, and remained elevated in the old rats for 28 days. In summary, either a diminished ability to downregulate myogenin and MyoD mRNAs in regenerating muscle occurs in old rat muscles, or the continuing myogenic effort includes elevated expression of these mRNAs.

  14. Developmental Vitamin D3 deficiency alters the adult rat brain.

    PubMed

    Féron, F; Burne, T H J; Brown, J; Smith, E; McGrath, J J; Mackay-Sim, A; Eyles, D W

    2005-03-15

    There is growing evidence that Vitamin D(3) (1,25-dihydroxyvitamin D(3)) is involved in brain development. We have recently shown that the brains of newborn rats from Vitamin D(3) deficient dams were larger than controls, had increased cell proliferation, larger lateral ventricles, and reduced cortical thickness. Brains from these animals also had reduced expression of nerve growth factor (NGF) and glial cell line-derived neurotrophic factor. The aim of the current study was to examine if there were any permanent outcomes into adulthood when the offspring of Vitamin D(3) deficient dams were restored to a normal diet. The brains of adult rats were examined at 10 weeks of age after Vitamin D(3) deficiency until birth or weaning. Compared to controls animals that were exposed to transient early Vitamin D(3) deficiency had larger lateral ventricles, reduced NGF protein content, and reduced expression of a number genes involved in neuronal structure, i.e. neurofilament or MAP-2 or neurotransmission, i.e. GABA-A(alpha4). We conclude that transient early life hypovitaminosis D(3) not only disrupts brain development but leads to persistent changes in the adult brain. In light of the high incidence of hypovitaminosis D(3) in women of child-bearing age, the public health implications of these findings warrant attention. PMID:15763180

  15. Decline of taste sensitivity in protein deficient adult rats.

    PubMed

    Ohara, I; Tabuchi, R; Kimura, M; Itokawa, Y

    1995-05-01

    The influence of dietary protein levels on taste sensitivity was studied in adult rats. Low protein diets of 0.0, 2.5, or 5.0% purified egg protein (PEP) were fed to animals for 28 days. Two bottle choice preference tests between aqueous solutions of either 2, 9, 17, or 86 mM sodium chloride and deionized water were conducted in an ascending order on days 14, 16, 18, and 20. Urine samples were collected for zinc and creatinine analysis. Blood samples were also collected for measuring serum zinc and creatinine concentrations. Scanning electron microscopy was performed to observe rats' tongue epithelia. Protein free diet group showed significantly lower taste sensitivity and renal reabsorption rate than other protein containing diet groups, while serum zinc and creatinine concentrations, and creatinine clearance were not affected by dietary protein level. Degeneration of filiform papillae and imperforation of taste pore of fungiform papillae were observed in protein free diet group. This experiment implies at least 2.5% dietary protein is required to manifest normal taste function in the adult. PMID:7610145

  16. Decline of taste sensitivity in protein deficient adult rats.

    PubMed

    Ohara, I; Tabuchi, R; Kimura, M; Itokawa, Y

    1995-05-01

    The influence of dietary protein levels on taste sensitivity was studied in adult rats. Low protein diets of 0.0, 2.5, or 5.0% purified egg protein (PEP) were fed to animals for 28 days. Two bottle choice preference tests between aqueous solutions of either 2, 9, 17, or 86 mM sodium chloride and deionized water were conducted in an ascending order on days 14, 16, 18, and 20. Urine samples were collected for zinc and creatinine analysis. Blood samples were also collected for measuring serum zinc and creatinine concentrations. Scanning electron microscopy was performed to observe rats' tongue epithelia. Protein free diet group showed significantly lower taste sensitivity and renal reabsorption rate than other protein containing diet groups, while serum zinc and creatinine concentrations, and creatinine clearance were not affected by dietary protein level. Degeneration of filiform papillae and imperforation of taste pore of fungiform papillae were observed in protein free diet group. This experiment implies at least 2.5% dietary protein is required to manifest normal taste function in the adult.

  17. Acute behavioral toxicity of carbaryl and propoxur in adult rats.

    PubMed

    Ruppert, P H; Cook, L L; Dean, K F; Reiter, L W

    1983-04-01

    Motor activity and neuromotor function were examined in adult CD rats exposed to either carbaryl or propoxur, and behavioral effects were compared with the time course of cholinesterase inhibition. Rats received an IP injection of either 0, 2, 4, 6 or 8 mg/kg propoxur or 0, 4, 8, 16 or 28 mg/kg carbaryl in corn oil 20 min before testing. All doses of propoxur reduced 2 hr activity in a figure-eight maze, and crossovers and rears in an open field. For carbaryl, dosages of 8, 16 and 28 mg/kg decreased maze activity whereas 16 and 28 mg/kg reduced open field activity. In order to determine the time course of effects, rats received a single IP injection of either corn oil, 2 mg/kg propoxur or 16 mg/kg carbaryl, and were tested for 5 min in a figure-eight maze either 15, 30, 60, 120 or 240 min post-injection. Immediately after testing, animals were sacrificed and total cholinesterase was measured. Maximum effects of propoxur and carbaryl on blood and brain cholinesterase and motor activity were seen within 15 min. Maze activity had returned to control levels within 30 and 60 min whereas cholinesterase levels remained depressed for 120 and 240 min for propoxur and carbaryl, respectively. These results indicate that both carbamates decrease motor activity, but behavioral recovery occurs prior to that of cholinesterase following acute exposure.

  18. Effect of exposure to diazinon on adult rat's brain.

    PubMed

    Rashedinia, Marzieh; Hosseinzadeh, Hossein; Imenshahidi, Mohsen; Lari, Parisa; Razavi, Bibi Marjan; Abnous, Khalil

    2016-04-01

    Diazinon (DZN), a commonly used agricultural organophosphate insecticide, is one of the major concerns for human health. This study was planned to investigate neurotoxic effects of subacute exposure to DZN in adult male Wistar rats. Animals received corn oil as control and 15 and 30 mg/kg DZN orally by gastric gavage for 4 weeks. The cerebrum malondialdehyde and glutathione (GSH) contents were assessed as biomarkers of lipid peroxidation and nonenzyme antioxidants, respectively. Moreover, activated forms of caspase 3, -9, and Bax/Bcl-2 ratios were evaluated as key apoptotic proteins. Results of this study suggested that chronic administration of DZN did not change lipid peroxidation and GSH levels significantly in comparison with control. Also, the active forms of caspase 3 and caspase 9 were not significantly altered in DZN-treated rat groups. Moreover, no significant changes were observed in Bax and Bcl-2 ratios. This study indicated that generation of reactive oxygen species was probably modulated by intracellular antioxidant system. In conclusion, subacute oral administration of DZN did not alter lipid peroxidation. Moreover, apoptosis induction was not observed in rat brain.

  19. Effect of MPEP in Morris water maze in adult and old rats.

    PubMed

    Car, Halina; Stefaniuk, Radosław; Wiśniewska, Róza J

    2007-01-01

    The present investigation assessed the effects of 2-methyl-6-(phenylethynyl)-pyridine (MPEP) on acquisition and reference memory in the Morris water maze in young adult rats aged 3-month and old rats aged 26-month. MPEP reduced the swim speed of the young adult rats during acquisition, shortened the distance they covered and reduced their swim speed in the probe trial. The untreated old rats had impaired acquisition of spatial learning, shortened distance and a lower swim speed in the probe trial in comparison with young rats. MPEP did not influence the activity of the old rats in the water maze. In summary, MPEP did not influence acquisition of spatial learning and reference memory in the young adult and old rats.

  20. Purification and culture of adult rat dorsal root ganglia neurons.

    PubMed

    Delree, P; Leprince, P; Schoenen, J; Moonen, G

    1989-06-01

    To study the trophic requirements of adult rat dorsal root ganglia neurons (DRG) in vitro, we developed a purification procedure that yields highly enriched neuronal cultures. Forty to fifty ganglia are dissected from the spinal column of an adult rat. After enzymatic and mechanical dissociation of the ganglia, myelin debris are eliminated by centrifugation on a Percoll gradient. The resulting cell suspension is layered onto a nylon mesh with a pore size of 10 microns. Most of the neurons, the diameter of which ranged from 17 microns to greater than 100 microns, are retained on the upper surface of the sieve; most of the non-neuronal cells with a caliber of less than 10 microns after trypsinization go through it. Recovery of neurons is achieved by reversing the mesh onto a Petri dish containing culture medium. Neurons to non-neurons ratio is 1 to 10 in the initial cell suspension and 1 to 1 after separation. When these purified neurons are seeded at a density of 3,000 neurons/cm2 in 6 mm polyornithine-laminin (PORN-LAM) coated wells, neuronal survival (assessed by the ability to extend neurites), measured after 48 hr of culture, is very low (from 0 to 16%). Addition of nerve growth factor (NGF) does not improve neuronal survival. However, when neurons are cultured in the presence of medium conditioned (CM) by astrocytes or Schwann cells, 60-80% of the seeded, dye-excluding neurons survive. So, purified adult DRG neurons require for their short-term survival and regeneration in culture, a trophic support that is present in conditioned medium from PNS or CNS glia.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Immature rat Leydig cells are intrinsically less sensitive than adult Leydig cells to ethane dimethanesulfonate.

    PubMed

    Kelce, W R; Zirkin, B R; Ewing, L L

    1991-11-01

    Leydig cells from immature rat testes appear to be insensitive to doses of ethane-1,2-dimethanesulfonate (EDS) which eliminate Leydig cells from adult rat testes. We sought to determine whether this differential response to EDS is intrinsic to the Leydig cell or mediated by other intra- or extratesticular differences between adult and immature rats. To differentiate among these possibilities, Leydig cells were exposed to EDS (1) in vivo, (2) through in vitro testicular perfusion, or (3) in highly purified Leydig cell primary cultures. Four days after ip injections of 85 mg EDS/kg body wt Leydig cells were eliminated from testes of adult, but not immature rats. Total androgen production by testes perfused in vitro with 94 micrograms EDS/ml was dramatically reduced in adult, but not immature rats. Highly purified adult, but not immature, rat Leydig cells were far more sensitive to the effects of EDS on luteinizing hormone-stimulated androgen production (functional effects; apparent EC50 = 94 for adult and 407 micrograms/ml for immature rat Leydig cells) and on [35S]methionine incorporation (cytotoxic effects; apparent EC50 = 140 for adult and 1000 micrograms/ml for immature rat Leydig cells). Finally, the in vitro effects of EDS were both cell type and chemical specific. Since the differential response of adult and immature rat Leydig cells to EDS was manifest in vivo, during in vitro testicular perfusion, and in highly purified Leydig cell primary cultures, we conclude that immature rat Leydig cells are intrinsically less sensitive to the specific cytotoxic effects of EDS than adult rat Leydig cells.

  2. Expression of Lymphatic Markers in the Adult Rat Spinal Cord

    PubMed Central

    Kaser-Eichberger, Alexandra; Schroedl, Falk; Bieler, Lara; Trost, Andrea; Bogner, Barbara; Runge, Christian; Tempfer, Herbert; Zaunmair, Pia; Kreutzer, Christina; Traweger, Andreas; Reitsamer, Herbert A.; Couillard-Despres, Sebastien

    2016-01-01

    Under physiological conditions, lymphatic vessels are thought to be absent from the central nervous system (CNS), although they are widely distributed within the rest of the body. Recent work in the eye, i.e., another organ regarded as alymphatic, revealed numerous cells expressing lymphatic markers. As the latter can be involved in the response to pathological conditions, we addressed the presence of cells expressing lymphatic markers within the spinal cord by immunohistochemistry. Spinal cord of young adult Fisher rats was scrutinized for the co-expression of the lymphatic markers PROX1 and LYVE-1 with the cell type markers Iba1, CD68, PGP9.5, OLIG2. Rat skin served as positive control for the lymphatic markers. PROX1-immunoreactivity was detected in many nuclei throughout the spinal cord white and gray matter. These nuclei showed no association with LYVE-1. Expression of LYVE-1 could only be detected in cells at the spinal cord surface and in cells closely associated with blood vessels. These cells were found to co-express Iba1, a macrophage and microglia marker. Further, double labeling experiments using CD68, another marker found in microglia and macrophages, also displayed co-localization in the Iba1+ cells located at the spinal cord surface and those apposed to blood vessels. On the other hand, PROX1-expressing cells found in the parenchyma were lacking Iba1 or PGP9.5, but a significant fraction of those cells showed co-expression of the oligodendrocyte lineage marker OLIG2. Intriguingly, following spinal cord injury, LYVE-1-expressing cells assembled and reorganized into putative pre-vessel structures. As expected, the rat skin used as positive controls revealed classical lymphatic vessels, displaying PROX1+ nuclei surrounded by LYVE-1-immunoreactivity. Classical lymphatics were not detected in adult rat spinal cord. Nevertheless, numerous cells expressing either LYVE-1 or PROX1 were identified. Based on their localization and overlapping expression with

  3. Expression of Lymphatic Markers in the Adult Rat Spinal Cord.

    PubMed

    Kaser-Eichberger, Alexandra; Schroedl, Falk; Bieler, Lara; Trost, Andrea; Bogner, Barbara; Runge, Christian; Tempfer, Herbert; Zaunmair, Pia; Kreutzer, Christina; Traweger, Andreas; Reitsamer, Herbert A; Couillard-Despres, Sebastien

    2016-01-01

    Under physiological conditions, lymphatic vessels are thought to be absent from the central nervous system (CNS), although they are widely distributed within the rest of the body. Recent work in the eye, i.e., another organ regarded as alymphatic, revealed numerous cells expressing lymphatic markers. As the latter can be involved in the response to pathological conditions, we addressed the presence of cells expressing lymphatic markers within the spinal cord by immunohistochemistry. Spinal cord of young adult Fisher rats was scrutinized for the co-expression of the lymphatic markers PROX1 and LYVE-1 with the cell type markers Iba1, CD68, PGP9.5, OLIG2. Rat skin served as positive control for the lymphatic markers. PROX1-immunoreactivity was detected in many nuclei throughout the spinal cord white and gray matter. These nuclei showed no association with LYVE-1. Expression of LYVE-1 could only be detected in cells at the spinal cord surface and in cells closely associated with blood vessels. These cells were found to co-express Iba1, a macrophage and microglia marker. Further, double labeling experiments using CD68, another marker found in microglia and macrophages, also displayed co-localization in the Iba1+ cells located at the spinal cord surface and those apposed to blood vessels. On the other hand, PROX1-expressing cells found in the parenchyma were lacking Iba1 or PGP9.5, but a significant fraction of those cells showed co-expression of the oligodendrocyte lineage marker OLIG2. Intriguingly, following spinal cord injury, LYVE-1-expressing cells assembled and reorganized into putative pre-vessel structures. As expected, the rat skin used as positive controls revealed classical lymphatic vessels, displaying PROX1+ nuclei surrounded by LYVE-1-immunoreactivity. Classical lymphatics were not detected in adult rat spinal cord. Nevertheless, numerous cells expressing either LYVE-1 or PROX1 were identified. Based on their localization and overlapping expression with

  4. Dietary restriction alters fine motor function in rats.

    PubMed

    Smith, Lori K; Metz, Gerlinde A

    2005-08-01

    A number of standard behavioral tasks in animal research utilize food rewards for positive reinforcement. In order to enhance the motivation to participate in these tasks, animals are usually placed on a restricted diet. While dietary restriction (DR) has been shown to have beneficial effects on recovery after brain injury, life span and aging processes, it might also represent a stressor. Since stress can influence a broad range of behaviors, the purpose of this study was to assess whether DR may have similar effects on skilled movement. Adult male Long-Evans rats were trained and tested in a skilled reaching task both prior to and during a mild food restriction regimen that maintained their body weights at 90-95% of baseline weight for eight days. The observations revealed that DR decreased reaching success and increased the number of attempts to grasp a single food pellet. The animals appeared to be more frantic when attempting to reach for food pellets, and the time taken to reach for 20 pellets decreased following the onset of DR. A second experiment investigating behaviors that do not require food rewards, including a ladder rung walking task and an open field test, confirmed that rats on DR display deficits in skilled movements and are hyperactive. These findings suggest that results obtained in motor tasks using food rewards need to be interpreted with caution. The findings are discussed with respect to stress associated with DR. PMID:16045945

  5. Polygonal networks, "geodomes", of adult rat hepatocytes in primary culture.

    PubMed

    Mochizuki, Y; Furukawa, K; Mitaka, T; Yokoi, T; Kodama, T

    1988-01-01

    Polygonal networks, "geodomes", in cultured hepatocytes of adult rats were examined by both light and electron microscopy. On light microscopical examinations of specimens stained with Coomassie blue after the treatment with Triton X-100, the networks were detected 5 days after culture, which consisted of triangles arranged mainly in hexagonal patterns. They surrounded main cell body, looking like a headband, or were occasionally situated over nuclei, looking like a geodesic dome. Scanning electron microscopical observations after Triton treatment revealed that these structures were located underneath surface membrane. Transmission electron microscopical investigations revealed that the connecting fibers of networks consisted of microfilaments which radiated in a compact bundle from electron-dense vertices. PMID:3396075

  6. Cysteamine reduces serum gonadotropin concentrations in adult male rats.

    PubMed

    Badger, T M; Sagar, S M; Millard, W J; Martin, J B; Rosenblum, P

    1982-01-18

    We have examined the effects of cysteamine on the hypothalamic-pituitary-gonadal axis of the adult male rat. A single subcutaneous injection of cysteamine (300 mg/kg) reduces significantly (p less than or equal to 0.05 serum concentrations of LH, FSH and T. Cysteamine blocked LH secretion induced by castration and administration of naloxone and LHRH. Neither acute nor chronic treatment (7 days) altered the hypothalamic LHRH content. These results suggest that cysteamine acts to reduce pituitary responsiveness to LHRH, resulting in lower mean serum gonadotropin and testosterone concentrations. It is possible, however, that cysteamine acts also at the hypothalamus to reduce LHRH secretion and/or at the testes to reduce testosterone release.

  7. Respiratory autoresuscitation following severe acute hypoxemia in anesthetized adult rats.

    PubMed

    Krause, A; Nowak, Z; Srbu, R; Bell, H J

    2016-10-01

    In the present study we investigated the pattern and efficacy of respiratory autoresuscitation in spontaneously breathing adult male rats across three separate anesthetic backgrounds. Each animal was administered one of three injectable anesthetics to achieve a surgical plane of anesthesia: ketamine-xylazine (KET, n=10), pentobarbital (PEN, n=10), or urethane (URE, n=10). Animals were tracheostomized and equipped with a femoral artery catheter to record airflow and arterial pressures. In response to a bout of breathing anoxic air, none of the 10 URE animals were able to mount a successful autoresuscitation response. In contrast, all KET and PEN animals survived all four consecutive anoxic exposures, restoring eupneic breathing in all cases. Moreover, only 4/10 URE animals expressed gasping breaths following the onset of respiratory arrest, and these were temporally delayed (p<0.001) and much smaller in volume (P≤0.012) compared to KET and PEN animals. URE animals showed no clear aberrations in their cardiovascular responses to anoxia, with the exception of lower arterial pulse pressures compared to either KET or PEN animals at specific points following RA. Ketamine-xylazine and pentobarbital anesthesia can be reliably and effectively used to create models for the study of autoresuscitation in adult rats. In contrast, urethane causes catastrophic failure of respiratory autoresuscitation, by delaying or outright preventing the elaboration of gasping breaths following anoxia-induced respiratory arrest. The neuronal and synaptic alterations accompanying urethane anesthesia may therefore provide a means of understanding potential pathological alterations in rhythm generation that can predispose the respiratory control system to failed autoresuscitation following an episode of acute severe hypoxemia. PMID:27378495

  8. Astaxanthin reduces ischemic brain injury in adult rats.

    PubMed

    Shen, Hui; Kuo, Chi-Chung; Chou, Jenny; Delvolve, Alice; Jackson, Shelley N; Post, Jeremy; Woods, Amina S; Hoffer, Barry J; Wang, Yun; Harvey, Brandon K

    2009-06-01

    Astaxanthin (ATX) is a dietary carotenoid of crustaceans and fish that contributes to their coloration. Dietary ATX is important for development and survival of salmonids and crustaceans and has been shown to reduce cardiac ischemic injury in rodents. The purpose of this study was to examine whether ATX can protect against ischemic injury in the mammalian brain. Adult rats were injected intracerebroventricularly with ATX or vehicle prior to a 60-min middle cerebral artery occlusion (MCAo). ATX was present in the infarction area at 70-75 min after onset of MCAo. Treatment with ATX, compared to vehicle, increased locomotor activity in stroke rats and reduced cerebral infarction at 2 d after MCAo. To evaluate the protective mechanisms of ATX against stroke, brain tissues were assayed for free radical damage, apoptosis, and excitoxicity. ATX antagonized ischemia-mediated loss of aconitase activity and reduced glutamate release, lipid peroxidation, translocation of cytochrome c, and TUNEL labeling in the ischemic cortex. ATX did not alter physiological parameters, such as body temperature, brain temperature, cerebral blood flow, blood gases, blood pressure, and pH. Collectively, our data suggest that ATX can reduce ischemia-related injury in brain tissue through the inhibition of oxidative stress, reduction of glutamate release, and antiapoptosis. ATX may be clinically useful for patients vulnerable or prone to ischemic events. PMID:19218497

  9. Astaxanthin reduces ischemic brain injury in adult rats.

    PubMed

    Shen, Hui; Kuo, Chi-Chung; Chou, Jenny; Delvolve, Alice; Jackson, Shelley N; Post, Jeremy; Woods, Amina S; Hoffer, Barry J; Wang, Yun; Harvey, Brandon K

    2009-06-01

    Astaxanthin (ATX) is a dietary carotenoid of crustaceans and fish that contributes to their coloration. Dietary ATX is important for development and survival of salmonids and crustaceans and has been shown to reduce cardiac ischemic injury in rodents. The purpose of this study was to examine whether ATX can protect against ischemic injury in the mammalian brain. Adult rats were injected intracerebroventricularly with ATX or vehicle prior to a 60-min middle cerebral artery occlusion (MCAo). ATX was present in the infarction area at 70-75 min after onset of MCAo. Treatment with ATX, compared to vehicle, increased locomotor activity in stroke rats and reduced cerebral infarction at 2 d after MCAo. To evaluate the protective mechanisms of ATX against stroke, brain tissues were assayed for free radical damage, apoptosis, and excitoxicity. ATX antagonized ischemia-mediated loss of aconitase activity and reduced glutamate release, lipid peroxidation, translocation of cytochrome c, and TUNEL labeling in the ischemic cortex. ATX did not alter physiological parameters, such as body temperature, brain temperature, cerebral blood flow, blood gases, blood pressure, and pH. Collectively, our data suggest that ATX can reduce ischemia-related injury in brain tissue through the inhibition of oxidative stress, reduction of glutamate release, and antiapoptosis. ATX may be clinically useful for patients vulnerable or prone to ischemic events.

  10. Course of motor recovery following ventrolateral spinal cord injury in the rat.

    PubMed

    Webb, Aubrey A; Muir, Gillian D

    2004-11-01

    The purpose of this study was to determine the importance of the pathways running in the ventrolateral spinal funiculus for overground locomotion in adult, freely behaving rats. Left-sided ventrolateral cervical spinal cord injury was performed in adult female Long-Evans rats. The behavioural abilities of these animals were analyzed at 2 days, and weekly for up to 5.5 weeks following spinal cord injury. Behavioural testing consisted of Von Frey filament testing, ladder walking, a paw usage task, and the assessment of ground reaction forces during unrestrained trotting. Animals with injury to the left ventrolateral cervical spinal cord did not develop enhanced sensitivity to pedal mechanical stimulation. At 2 days following injury, animals had impaired skilled locomotion as indicated by increased number of footslips during ladder walking. At 2 days, these animals also used both limbs together more often for support while rearing, while using the forelimb ipsilateral to the injury less than did uninjured animals. Ground reaction force determination revealed that animals tend to bear less weight on the forelimb and hindlimb ipsilateral to the spinal cord injury 2 days after injury. All animals recovered normal or near normal sensorimotor abilities although subtle asymmetries in ground reaction forces were detectable at 5.5 weeks following spinal cord injury. These results suggest that axons in the ventrolateral spinal funiculi contribute to limb movements during exploration and locomotion but their roles can be served by other pathways after ventrolateral spinal injury. PMID:15325779

  11. Comparison of electroretinographic responses between two different age groups of adult Dark Agouti rats

    PubMed Central

    Fu, Lin; Lo, Amy Cheuk Yin; Lai, Jimmy Shiu Ming; Shih, Kendrick Co

    2015-01-01

    AIM To describe and compare the differences in electroretinographic responses between two different age groups of adult Dark Agouti (DA) rats and to better understand the effect of age on retinal histology and function. METHODS The electroretinographic responses of two different age groups of adult DA rats were compared. Animals were divided into younger adult DA rats 10-12wk (n=8) and older adult DA rats 17-19wk (n=8). Full field electroretinography (ERG) was recorded simultaneously from both eyes after dark adaption and light adaption and parameters including the positive scotopic threshold response (pSTR), negative scotopic threshold response (nSTR), scotopic a-wave, b-wave, photopic a-wave, b-wave and photopic negative response (PhNR) were compared between groups. RESULTS The older adult rats displayed lower stimulation thresholds of the STRs (pSTR and nSTR) and higher amplitudes of pSTR, scotopic a-wave and b-wave, photopic b-wave and PhNR amplitudes, with shorter implicit times. Photopic a-wave amplitudes were however higher in the younger adult rats. CONCLUSION In summary, for the rod system, photoreceptor, bipolar cell and RGC activity was enhanced in the older adult rats. For the cone system, RGC and bipolar cell activity was enhanced, while photoreceptor activity was depressed in the older adult rats. Such age-related selective modification of retinal cell function needs to be considered when conducting ophthalmic research in adult rats. PMID:26558198

  12. Interaction of ambient temperature and microwave power density on schedule-controlled behavior in the rat

    SciTech Connect

    Gage, M.I.; Guyer, W.M.

    1985-01-01

    Most guidelines of microwave exposure do not explicitly address effects of ambient temperature. This experiment revealed that ambient temperature potentiates the behavioral effects of intensity of irradiation. Sixty-four adult male Long-Evans rats were trained to insert their heads into a food cup to obtain food pellets on a 1-min variable-interval schedule of reinforcement. Two groups of four rats each were then exposed to 2450-MHz CW microwaves for 15.5 hours under one of the following eight combinations of power density and air temperature: 8 or 14 m/cm. sq. at 22 C; 0, 8, or 14 mW/cm. sq. at 26 C; and 0, 8, or 14 mW/cm. sq. at 30 C (relative humidity was 50% in all cases). Response rate of each rat following exposure was compared with its control rate at 0 mW/cm. sq. and 22 C. After exposure at 8 mW/cm. sq., response rates were reduced by a mean of 13.8% at 22 C, 27.5% at 26 C, and 77.5% at 30 C. After exposure at 14 mW/cm. sq., rates were reduced by a mean of 21.1% at 22 C, 43.7% at 26 C, and 80.0% at 30 C. In the absence of microwaves the higher temperatures caused only slight decreases in response rate.

  13. Neonatal injections of methoxychlor decrease adult rat female reproductive behavior.

    PubMed

    Bertolasio, Jennifer; Fyfe, Susanne; Snyder, Ben W; Davis, Aline M

    2011-12-01

    Methoxychlor (MXC), a commonly used pesticide, has been labeled as an endocrine disruptor. To evaluate the impact of neonatal exposure to MXC on female reproduction, female Sprague-Dawley rats were given subcutaneous injections on postnatal days 1, 3, and 5. The injections contained 1.0mg MXC, 2.0mg MXC, 10 μg 17β-estradiol benzoate (positive control), or sesame oil (vehicle). The injections of MXC had no effect on anogenital distance or day of vaginal opening. Treatment with either 2.0mg MXC or estradiol significantly increased the total number of days with vaginal keratinization. Treatment with MXC had no effect on ability to exhibit a mating response as an adult female, although the high dose MXC (2.0) and the positive control (estradiol) animals demonstrated a decrease in degree of receptivity, a decrease in proceptive behavior and an increase in rejection behavior. These data suggest that higher doses of MXC given directly to pups during the neonatal period can act as an estrogen and alter aspects of the nervous system, impacting adult reproductive characteristics.

  14. Effect of MDMA (ecstasy) on activity and cocaine conditioned place preference in adult and adolescent rats.

    PubMed

    Aberg, Maria; Wade, Dean; Wall, Erin; Izenwasser, Sari

    2007-01-01

    MDMA (ecstasy) is a drug commonly used in adolescence, and many users of MDMA also use other illicit drugs. It is not known whether MDMA during adolescence alters subsequent responses to cocaine differently than in adults. This study examined the effects of MDMA in adolescent and adult rats on cocaine conditioned reward. At the start of these experiments, adolescent rats were at postnatal day (PND) 33 and adult rats at PND 60. Each rat was treated for 7 days with MDMA (2 or 5 mg/kg/day or vehicle) and locomotor activity was measured. Five days later cocaine conditioned place preference (CPP) was begun. Rats were trained for 3 days, in the morning with saline and in the afternoon with 10 mg/kg cocaine in 30 min sessions, and tested on the fourth day. MDMA stimulated activity in both age groups, but with a greater effect in the adult rats. Sensitization to the locomotor-stimulant effects of the lower dose of MDMA occurred in adult rats and in both groups to the higher dose. Cocaine did not produce a CPP in vehicle-treated adolescent rats, but a significant CPP was observed subsequent to treatment with MDMA. In contrast, cocaine-induced CPP was diminished after MDMA in adult rats. These effects were still evident 2 weeks later upon retest. Thus, under the present conditions, MDMA increased cocaine conditioned reward in adolescent and decreased it in adult rats. These findings suggest that exposure to MDMA during this critical developmental period may carry a greater risk than during adulthood and that male adolescents may be particularly vulnerable to the risk of stimulant abuse after use of MDMA.

  15. The effect of gender, sexual maturation and xenobiotic treatment on the formation of hydroxymethyl metabolites from 7, 12-dimethylbenz[a]anthracene in rat liver microsomes.

    PubMed

    Boyle, S P; Craft, J A

    2000-09-30

    The effects of age, gender, strain, phenobarbital (PB) treatment and pituitary influence on the regioselective metabolism of 7, 12-dimethylbenz[a]anthracene to hydroxmethyl metabolites were investigated. Studies used hepatic microsomal membranes from immature and mature Long Evans (LE) rats and adult Hooded Lister (HL) animals. Hydroxymethyl metabolites were resolved by both normal and reverse phase HPLC with on-line diode array detection. The CYP isoform(s) responsible for oxidation at the 12 methyl position exhibited no gender or developmental regulation and the rate of formation was not altered following hypophysectomy. PB-treatment of adult rats caused a significant increase in the rate of formation of both male and female animals (29 and 41-fold, respectively) suggesting a major contribution from a PB-inducible isoform, such as CYP2B. The rate of formation of 7OHMe12MBA exhibited no gender dependency in immature animals but was 2-fold greater than that observed for 12OHMe7MBA suggesting that steric hindrance resulting from the adjacent 1,2 benzyl ring favours substrate oxidation at the 7-methyl position. Male predominant formation of 7OHMe12MBA was apparent following sexual maturation of the LE rats and was significantly reduced upon hypophysectomy suggesting the involvement of a male-specific GH dependent isoform e.g. CYP2C11.

  16. The effect of gender, sexual maturation and xenobiotic treatment on the formation of hydroxymethyl metabolites from 7, 12-dimethylbenz[a]anthracene in rat liver microsomes.

    PubMed

    Boyle, S P; Craft, J A

    2000-09-30

    The effects of age, gender, strain, phenobarbital (PB) treatment and pituitary influence on the regioselective metabolism of 7, 12-dimethylbenz[a]anthracene to hydroxmethyl metabolites were investigated. Studies used hepatic microsomal membranes from immature and mature Long Evans (LE) rats and adult Hooded Lister (HL) animals. Hydroxymethyl metabolites were resolved by both normal and reverse phase HPLC with on-line diode array detection. The CYP isoform(s) responsible for oxidation at the 12 methyl position exhibited no gender or developmental regulation and the rate of formation was not altered following hypophysectomy. PB-treatment of adult rats caused a significant increase in the rate of formation of both male and female animals (29 and 41-fold, respectively) suggesting a major contribution from a PB-inducible isoform, such as CYP2B. The rate of formation of 7OHMe12MBA exhibited no gender dependency in immature animals but was 2-fold greater than that observed for 12OHMe7MBA suggesting that steric hindrance resulting from the adjacent 1,2 benzyl ring favours substrate oxidation at the 7-methyl position. Male predominant formation of 7OHMe12MBA was apparent following sexual maturation of the LE rats and was significantly reduced upon hypophysectomy suggesting the involvement of a male-specific GH dependent isoform e.g. CYP2C11. PMID:11033228

  17. Estrogen Receptor-Selective Agonists Modulate Learning in Female Rats in a Dose- and Task-Specific Manner.

    PubMed

    Pisani, Samantha L; Neese, Steven L; Katzenellenbogen, John A; Schantz, Susan L; Korol, Donna L

    2016-01-01

    Estrogens are well known for their enhancing effects on hippocampus-sensitive cognition. However, estrogens can also impair learning and memory, particularly the acquisition of striatum-sensitive tasks. These cognitive shifts appear to be mediated through local estrogen receptor (ER) activation in each neural structure, but little information is known regarding which specific ER subtypes drive the opposing effects on learning. Elucidating the mnemonic roles of discrete ER subtypes is essential for predicting how treatments with distinct ER pharmacology such as drugs, hormone therapies, and phytoestrogen supplements affect cognitive abilities in and thus the daily lives of the women who take them. The present study examined the effects of the ERα-selective compound propyl pyrazole triol and the ERβ-selective compounds diarylpropionitrile and Br-ERb-041 on place and response learning in young adult female rats. Long-Evans rats were ovariectomized and maintained on phytoestrogen-free chow for 3 weeks before behavioral training, with treatments administered via subcutaneous injection 48 and 24 hours before testing. A dose-response paradigm was used, with each compound tested at 4 different doses in separate groups of rats. Propyl pyrazole triol, diarylpropionitrile, and Br-ERb-041 all enhanced place learning and impaired response learning, albeit with distinct dose-response patterns for each compound and task. These results are consistent with the detection of ERα and ERβ in the hippocampus and striatum and suggest that learning is modulated via activation of either ER subtype. PMID:26465198

  18. Nocturnal food-related hyperdipsia in the adult spontaneously hypertensive rat.

    PubMed

    Kraly, F S; Moore, A F; Miller, L A; Drexler, A

    1982-05-01

    Male adult spontaneously hypertensive rats (SHR) ate the same but drank more and had a higher water to food ratio (W:F) than did Wistar-Kyoto (WKY) rats in 24-hr when they had continuous access to standard laboratory pellets and tap water. When rats ate in the day phase of a 12:12 light/dark cycle after 24-hr food deprivation, SHR rats ate and drank the same ad did WKY rats in a 60-min test. When the same rats ate at night after 24-hr food deprivation, however, SHR rats were hyperdipsic: They ate the same as did WKY rats, but SHR rats drank more and had a higher W:F. This relative hyperdipsia reflected the increased ability of ingestion of food to stimulate drinking in SHR, because when food was absent for a 60-min test at night SHR drank the same as did WKY rats. Three dipsogens which are candidate components for eating-elicited drinking in the rat, cellular dehydration, histamine and angiotensin II, elicited drinking differentially in SHR and WKY rats: SHR drank more than did WKY rats in response to (1) cellular dehydration produced by IP hypertonic saline, (2) large doses of SC histamine, and (3) SC angiotensin II. These results demonstrate that SHR exhibit a nocturnal food-related hyperdipsia which may reflect differential sensitivity to stimuli important for eating-elicited drinking such as increased osmolality and endogenous histamine or angiotensin.

  19. Differences in Response Initiation and Behavioral Flexibility Between Adolescent and Adult Rats

    PubMed Central

    Simon, Nicholas W.; Gregory, Timothy A.; Wood, Jesse; Moghaddam, Bita

    2014-01-01

    Adolescence is a period of increased vulnerability to psychiatric illnesses such as addiction, mood disorders, and schizophrenia. Rats provide a useful animal model for investigating the differences in behavior and biology between adults and adolescents that stem from ongoing brain development. We developed the Cued Response Inhibition Task, or CRIT, to assess response inhibition and initiation processes by measuring the ability of rodents to withhold a response during an inhibitory cue and then to respond promptly after cue termination. We found no difference between adult and adolescent rats in the ability to appropriately inhibit a response during cue presentation. Adolescents, however, were unable to initiate a response as quickly as adults after cue termination. Further, we observed that this difference in responding was abolished after adolescent rats aged to adulthood with no additional training. In a separate experiment, adult and adolescent rats were trained in CRIT and then trained in another protocol in which the response inhibitory cue from CRIT was used as a Pavlovian cue predictive of reward. Adolescents demonstrated more reward-seeking behavior during the previously inhibitory Pavlovian cue than adults, indicative of greater behavioral flexibility. Taken together, these data suggest that, compared with adults, adolescent rats (a) are less able to initiate a response after response inhibition, (b) equally inhibit behavioral responses, and (c) are more adept at flexibly switching behavioral patterns. Furthermore, this study characterizes a task that is well suited for future pharmacological and electrophysiological investigations for assessing neuronal processing differences between adolescents and adults. PMID:23398439

  20. Accumulation of glycogen in axotomized adult rat facial motoneurons.

    PubMed

    Takezawa, Yosuke; Baba, Otto; Kohsaka, Shinichi; Nakajima, Kazuyuki

    2015-06-01

    This study biochemically determined glycogen content in the axotomized facial nucleus of adult rats up to 35 days postinsult. The amounts of glycogen in the transected facial nucleus were significantly increased at 5 days postinsult, peaked at 7 days postinsult, and declined to the control levels at 21-35 days postinsult. Immunohistochemical analysis with antiglycogen antibody revealed that the quantity of glycogen granules in the axotomized facial nucleus was greater than that in the control nucleus at 7 days postinjury. Dual staining methods with antiglycogen antibody and a motoneuron marker clarified that the glycogen was localized mainly in motoneurons. Immunoblotting and quantification analysis revealed that the ratio of inactive glycogen synthase (GS) to total GS was significantly decreased in the injured nucleus at about 1-3 days postinsult and significantly increased from 7 to 14 days postinsult, suggesting that glycogen is actively synthesized in the early period postinjury but suppressed after 7 days postinsult. The enhanced glycogen at about 5-7 days postinsult is suggested to be responsible for the decrease in inactive GS levels, and the decrease of glycogen after 7 days postinsult is considered to be caused by increased inactive GS levels and possibly the increase in active glycogen phosphorylase.

  1. Regional haemodynamic effects of noradrenaline injected into the hypothalamic paraventricular nuclei of conscious, unrestrained rats: possible mechanisms of action.

    PubMed

    Bachelard, H; Harland, D; Gardiner, S M; Kemp, P A; Bennett, T

    1992-01-01

    The cardiovascular effects of noradrenaline bilaterally injected into the hypothalamic paraventricular nuclei were investigated in conscious, unrestrained Long-Evans rats and homozygous, vasopressin-deficient Brattleboro rats, chronically instrumented with pulsed Doppler probes for measurement of regional haemodynamics. In Long-Evans rats, incremental doses of noradrenaline (0.01-10 nmol) caused dose-related increases in blood pressure and a substantial, dose-related, superior mesenteric vasoconstriction. These changes were accompanied by bradycardia and reductions in renal and hind-quarter vascular conductances. In Brattleboro rats, noradrenaline (10 nmol) had no effect on blood pressure, heart rate, or renal or superior mesenteric vascular conductances. However, there was a slight vasodilatation in the vascular bed of the hindquarters. In Long-Evans rats, intravenous pretreatment with phentolamine had no effect on the bradycardia but partly inhibited the pressor response to noradrenaline injected into the paraventricular nuclei. These effects were associated with a smaller superior mesenteric vasoconstriction and an abolition of the vasoconstriction in the hindquarters. Combined intravenous pretreatment with phentolamine and propranolol had no effect on the heart rate or pressor responses to noradrenaline injected into the paraventricular nuclei, but reduced the superior mesenteric vasoconstriction, potentiated the vasoconstriction in the hindquarters and eliminated the renal vasoconstriction. These results suggest that, in untreated Long-Evans rats, alpha-adrenoceptor-mediated constriction in the mesenteric vascular bed and beta-adrenoceptor-mediated dilatation in the vascular bed of the hindquarters have important influences on the pressor response to noradrenaline injected into the paraventricular nuclei. In the presence of the vasopressin V1-receptor antagonist, d(CH2)5[Tyr(Et)]DAVP, the pressor and heart rate responses to noradrenaline injected into the

  2. Voluntary exercise impairs initial delayed spatial alternation performance in estradiol treated ovariectomized middle-aged rats.

    PubMed

    Neese, Steven L; Korol, Donna L; Schantz, Susan L

    2013-09-01

    Estrogens differentially modulate behavior in the adult female rodent. Voluntary exercise can also impact behavior, often reversing age associated decrements in memory processes. Our research group has published a series of papers reporting a deficit in the acquisition of an operant working memory task, delayed spatial alternation (DSA), following 17β-estradiol treatment to middle-aged ovariectomized (OVX) rats. The current study examined if voluntary exercise could attenuate the 17β-estradiol induced deficits on DSA performance. OVX 12-month old Long-Evans rats were implanted with a Silastic capsule containing 17β-estradiol (10% in cholesterol: low physiological range) or with a blank capsule. A subset of the 17β-estradiol and OVX untreated rats were given free access to a running wheel in their home cage. All rats were tested for 40 sessions on the DSA task. Surprisingly, we found running wheel access to impair initial acquisition of the DSA task in 17β-estradiol treated rats, an effect not seen in OVX untreated rats given running wheel access. This deficit was driven by an increase in perseverative responding on a lever no longer associated with reinforcement. We also report for the first time a 17β-estradiol induced impairment on the DSA task following a long intertrial delay (18-sec), an effect revealed following more extended testing than in our previous studies (15 additional sessions). Overall, running wheel access increased initial error rate on the DSA task in 17β-estradiol treated middle-aged OVX rats, and failed to prevent the 17β-estradiol induced deficits in performance of the operant DSA task in later testing sessions.

  3. Adolescent and adult male spontaneous hyperactive rats (SHR) respond differently to acute and chronic methylphenidate (Ritalin).

    PubMed

    Barron, Elyssa; Yang, Pamela B; Swann, Alan C; Dafny, Nachum

    2009-01-01

    Eight groups of male adolescent and adult spontaneous hyperactive rats (SHR) were used in a dose response (saline, 0.6, 2.5, and 10 mg/kg) experiment of methylphenidate (MPD). Four different locomotor indices were recorded for 2 hours postinjection using a computerized monitoring system. Acutely, the 0.6 mg/kg dose of MPD did not elicit an increase in locomotor activity in either the adolescent or in the adult male SHR. The 2.5 and the 10.0 mg/kg doses increased activity in the adolescent and the adult rats. Chronically, MPD treatment when comparing adolescent and adult gave the following results: the 0.6 mg/kg dose of MPD failed to cause sensitization in the adolescent group but caused sensitization in the adult group, while the 2.5 and 10 mg/kg both caused sensitization in the adolescent and adult groups.

  4. Sensitivity to cholinergic drug treatments of aged rats with variable degrees of spatial memory impairment.

    PubMed

    Stemmelin, J; Cassel, J C; Will, B; Kelche, C

    1999-01-01

    As a first step, the present experiment aimed at characterizing learning and memory capabilities, as well as some motor and sensorimotor faculties, in aged (24-26.5 months) Long-Evans female rats. As a second step, a psychopharmacological approach was undertaken in order to examine the sensitivity of aged rats to muscarinic blockade and to cholinomimetic treatments. Young adult (3-5.5 months) and aged rats were tested for beam-walking performance, locomotor activity in the home cage and an open field, and spatial learning/memory performance in a water maze and a radial maze. Spontaneous alternation rates were assessed in a T-maze. Statistical analysis discriminated between aged rats showing moderate impairment (AMI) and those showing severe impairment (ASI) in the water maze test. Beside their different degrees of impairment in the water maze, AMI and ASI rats were similarly (no significant difference) impaired in beam-walking capabilities, home cage activity and radial maze performance. In the spontaneous alternation task aged rats were not impaired and, in the open-field test, AMI rats were hypoactive, but not as much as ASI rats. Neither of the cognitive deficits was correlated with a locomotor or a sensorimotor variable, or with the body weight. When tested in the radial maze, a low dose of scopolamine (0.1 mg/kg i.p.) produced memory impairments which were significant in AMI and ASI rats, but not in young rats. Combined injections of scopolamine and physostigmine (0.05 and 0.1 mg/kg) or tacrine (THA, 3 mg/kg) showed physostigmine (0.1 mg/kg) to compensate for the scopolamine-induced impairments only in AMI rats. whereas THA was efficient in both AMI and ASI rats. The results indicate: (i) that rats with different degrees of spatial memory impairment in the water maze are similarly hypersensitive to muscarinic blockade when tested in a radial maze test; and (ii) that under the influence of a dose of scopolamine which is subamnesic in young rats, aged rats

  5. Lycium barbarum polysaccharides promotes in vivo proliferation of adult rat retinal progenitor cells

    PubMed Central

    Wang, Hua; Lau, Benson Wui-Man; Wang, Ning-li; Wang, Si-ying; Lu, Qing-jun; Chang, Raymond Chuen-Chung; So, Kwok-fai

    2015-01-01

    Lycium barbarum is a widely used Chinese herbal medicine prescription for protection of optic nerve. However, it remains unclear regarding the effects of Lycium barbarum polysaccharides, the main component of Lycium barbarum, on in vivo proliferation of adult ciliary body cells. In this study, adult rats were intragastrically administered low- and high-dose Lycium barbarum polysaccharides (1 and 10 mg/kg) for 35 days and those intragastrically administered phosphate buffered saline served as controls. The number of Ki-67-positive cells in rat ciliary body in the Lycium barbarum polysaccharides groups, in particular low-dose Lycium barbarum polysaccharides group, was significantly greater than that in the phosphate buffered saline group. Ki-67-positive rat ciliary body cells expressed nestin but they did not express glial fibrillary acidic protein. These findings suggest that Lycium barbarum polysaccharides can promote the proliferation of adult rat retinal progenitor cells and the proliferated cells present with neuronal phenotype. PMID:26889185

  6. Effects of long-term methylphenidate treatment in adolescent and adult rats on hippocampal shape, functional connectivity and adult neurogenesis.

    PubMed

    van der Marel, K; Bouet, V; Meerhoff, G F; Freret, T; Boulouard, M; Dauphin, F; Klomp, A; Lucassen, P J; Homberg, J R; Dijkhuizen, R M; Reneman, L

    2015-11-19

    Methylphenidate (MPH) is a widely prescribed stimulant drug for the treatment of attention deficit hyperactivity disorder (ADHD) in children and adolescents. Its use in this age group raises concerns regarding the potential interference with ongoing neurodevelopmental processes. Particularly the hippocampus is a highly plastic brain region that continues to develop postnatally and is involved in cognition and emotional behavior, functions known to be affected by MPH. In this study, we assessed whether hippocampal structure and function were affected by chronic oral MPH treatment and whether its effects were different in adolescent or adult rats. Using behavioral testing, resting-state functional MRI, post-mortem structural magnetic resonance imaging (MRI), and immunohistochemistry, we assessed MPH's effects on recognition memory, depressive-like behavior, topological features of functional connectivity networks, hippocampal shape and markers for hippocampal neurogenesis and proliferation. Object recognition memory was transiently impaired in adolescent treated rats, while in animals treated during adulthood, increased depressive-like behavior was observed. Neurogenesis was increased in adolescent treated rats, whereas cell proliferation was decreased following adult treatment. Adolescent treated rats showed inward shape deformations adjacent to ventral parahippocampal regions known to be involved in recognition memory, whereas such deformations were not observed in adult treated animals. Irrespective of the age of treatment, MPH affected topological features of ventral hippocampal functional networks. Thus, chronic oral treatment with a therapeutically relevant dose of MPH preferentially affected the ventral part of the hippocampus and induced contrasting effects in adolescent and adult rats. The differences in behavior were paralleled by opposite effects on adult neurogenesis and granule cell proliferation.

  7. TESTING FOR DEPARTURES FROM ADDITIVITY FOR A 2:1 MIXTURE OF CHLORPYRIFOS AND CARBARYL ON CHOLINESTERASE ACTIVITY IN BRAIN, PLASMA, AND RED BLOOD CELLS OF LONG EVANS RATS.

    EPA Science Inventory

    Detecting and characterizing interactions among chemicals is an important environmental issue. This study was conducted to test for the existence of a significant departure from additivity for a mixture of two cholinesterase (ChE)-inhibiting pesticides: chlorpyrifos (CPF), an org...

  8. Gestational and Lactational Exposure to Ethinyl Estradiol, but not Bisphenol A, Decreases Androgen-Dependent Reproductive Organ Weights and Epididymal Sperm Abundance in the Male Long Evans Hooded Rat.

    EPA Science Inventory

    Many chemicals released into the environment are capable of disrupting normal sex steroid balance, including the oral contraceptive ethinyl estradiol (EE) and the plastic monomer bisphenol A (BPA). EE and BPA are reported to impair reproductive organ development in laboratory ani...

  9. AN ASSESSMENT OF THE EFFECTS OF GESTATIONAL AND LACTATIONAL EXPOSURE TO ETHINYL ESTRADIOL (EE) AND BISPHENOL A (BPA) ON REPRODUCTIVE MORPHOLOGY AND BEHAVIOR IN THE FEMALE LONG EVANS HOODED RAT

    EPA Science Inventory

    Anthropogenic estrogens are pervasive in the environment. The effects of these 'xenoestrogens' are controversial in humans, although there is a clear indication that some fish species are adversely affected in contaminated ecosystems. The current project focuses on the effects ...

  10. BRAIN CHOLINESTERASE INHIBITION AND DEPRESSION OF THE PHOTIC AFTER DISCHARGE (PHAD) OF FLASH EVOKED POTENTIALS (FEPS) IN LONG EVANS RATS FOLLOWING ACUTE OR REPEATED EXPOSURES TO A MIXTURE OF CARBARYL AND PROPOXUR.

    EPA Science Inventory

    Carbaryl and propoxur are N-methyl carbamate pesticides (NMCs) which are part of the EPA’s cumulative risk assessments for NMCs. These NMCs inhibit cholinesterase (ChE) activity and may lead to cholinergic disruption of CNS function. We used decreases in the PhAD of FEPs to indic...

  11. AN ASSESSMENT OF THE EFFECTS OF GESTATIONAL AND LACTATIONAL EXPOSURE TO ETHINYL ESTRADIOL (EE) AND BISPHENOL A (BPA) ON REPRODUCTIVE MORPHOLOGY AND BEHAVIOR IN FEMALE AND MALE LONG EVANS HOODED RAT

    EPA Science Inventory

    Anthropogenic estrogens are pervasive in the environment. Although the effects of these 'xenoestrogens' are controversial in humans, some fish species are adversely affected in contaminated ecosystems. The current project focuses on the effects of developmental exposure to two ...

  12. Differential Effects of Acute Alcohol on EEG and Sedative Responses in Adolescent and Adult Wistar Rats

    PubMed Central

    Pian, Jerry P.; Criado, Jose R.; Walker, Brendan M.; Ehlers, Cindy L.

    2008-01-01

    Age-related developmental differences in sensitivity to the acute effects of alcohol may play an important role in the development of alcoholism. The present study was designed to evaluate the acute effects of alcohol on cortical electroencephalogram (EEG) in adolescent (P36) and adult (P78) Wistar rats. Five minutes of EEG was recorded after administration of 0, 0.75 or 1.5 g/kg alcohol. The righting reflex was performed to measure the sedative effects of alcohol (3.5 g/kg) and total sleeping time for each rat. Our results showed that alcohol (1.5 g/kg) increased power in the 1–2 Hz band and decreased the power in the 32–50 Hz band in the parietal cortical region of adolescent rats. Alcohol (1.5 g/kg) also increased stability of the EEG power in the slow-wave frequency bands (2–4 Hz, 4–6 Hz, and 6–8 Hz) of adolescent rats. In the frontal cortex of adult rats, but not in adolescent rats, alcohol (1.5 or 0.75 g/kg) decreased the power in the 16–32 Hz frequency band. Alcohol (1.5 g/kg) differentially increased power in a multiple of slow-wave frequency bands (2–4 Hz and 4–6 Hz) in the parietal cortex of adult rats as compared to adolescent rats. Adolescent rats were shown significantly shorter sleeping time and higher blood alcohol levels after regaining reflex than adult rats. Our results provide additional evidence of age-related differences in the effects of acute alcohol on cortical EEG, sedation and tolerance. PMID:18191821

  13. Daily patterns of ethanol drinking in peri-adolescent and adult alcohol-preferring (P) rats.

    PubMed

    Bell, Richard L; Rodd, Zachary A; Sable, Helen J K; Schultz, Jonathon A; Hsu, Cathleen C; Lumeng, Lawrence; Murphy, James M; McBride, William J

    2006-01-01

    Alcohol abuse among adolescents continues to be a major health problem for our society. Our laboratory has used the peri-adolescent alcohol-preferring, P, rat as an animal model of adolescent alcohol abuse. Even though peri-adolescent P rats consume more alcohol (g/kg/day) than their adult counterparts, it is uncertain whether their drinking is sufficiently aggregated to result in measurable blood ethanol concentrations (BECs). The objectives of this study were to examine daily alcohol drinking patterns of adolescent and adult, male and female P rats, and to determine whether alcohol drinking episodes were sufficiently aggregated to result in meaningful BECs. Male and female P rats were given 30 days of 24 h free-choice access to alcohol (15%, v/v) and water, with ad lib access to food, starting at the beginning of adolescence (PND 30) or adulthood (PND 90). Water and alcohol drinking patterns were monitored 22 h/day with a "lickometer" set-up. The results indicated that (a) peri-adolescent P rats consumed more water and total fluids than adult P rats, (b) female P rats consumed more water and total fluids than male P rats, (c) there were differences in alcohol, and water, licking patterns between peri-adolescent and adult and female and male P rats, (d) individual licking patterns revealed that alcohol was consumed in bouts often exceeding the amount required to self-administer 1 g/kg of alcohol, and (e) BECs at the end of the dark cycle, on the 30th day of alcohol access, averaged 50 mg%, with alcohol intakes during the last 1 to 2 h averaging 1.2 g/kg. Overall, these findings indicate that alcohol drinking patterns differ across the age and sex of P rats. This suggests that the effectiveness of treatments for reducing excessive alcohol intake may vary depending upon the age and/or sex of the subjects being tested.

  14. In vivo dermal absorption of pyrethroid pesticides in the rat.

    PubMed

    Hughes, Michael F; Edwards, Brenda C

    2016-01-01

    Exposure to pyrethroid pesticides is a potential cause for concern. The objective of this study was to examine the in vivo dermal absorption of bifenthrin, deltamethrin, and permethrin in the rat. Dorsal hair on adult male Long-Evans rats was removed. The next day, the skin was dosed with 1750 nmol (312.5 nmol/cm(2)) of radiolabeled (5 µCi) bifenthrin, deltamethrin, or permethrin in acetone. A nonoccluding plastic cover was glued over the dosing site. The animals were placed in metabolism cages to collect excreta. At 24 h postdosing, the skin was washed with soap and water, and rats in one group were euthanized and their tissues were collected. The skin was removed and tape stripped. The remaining animals were returned to the metabolism cages after the wash for 4 d. These rats were then euthanized and handled as already described. Excreta, wash, tape strips, tissues, and carcass were analyzed for pyrethroid-derived radioactivity. The wash and tape strips removed >50% of the dose and skin retained 9-24%. Cumulative radioactivity in excreta was 0.5-7% at 24 h and 3-26% at 120 h. Radioactivity in tissues was <0.3% of the dose, while carcass retained 2 to 5%. Assuming absorption equals cumulative recovery in skin (washed and tape stripped), excreta, tissues, and carcass, absorption was permethrin ~ bifenthrin > deltamethrin at 24 h and permethrin > deltamethrin > bifenthrin at 120 h. Using the parallelogram approach with published in vitro data, human dermal absorption of these pyrethroids was estimated to be <10% of the dose. PMID:26817658

  15. Fetal hypothalamic transplants into brain irradiated rats: Graft morphometry and host behavioral responses

    SciTech Connect

    Pearlman, S.H.; Rubin, P.; White, H.C.; Wiegand, S.J.; Gash, D.M. )

    1990-08-01

    This study was designed to test the hypothesis that neural implants can ameliorate or prevent some of the long-term changes associated with CNS irradiation. Using a rat model, the initial study focused on establishing motor, regulatory, and morphological changes associated with brain radiation treatments. Secondly, fetal hypothalamic tissue grafts were placed into the third ventricle of rats which had been previously irradiated. Adult male Long Evans rats received one of three radiation doses (15, 22.5, 30 Gy) or no radiation. Three days after irradiation, 7 animals in each dose group received an embryonic day 17 hypothalamic graft into the third ventricle while the remaining 8-9 animals in each group received injections of vehicle solution (sham). Few changes were observed in the 15 and 22.5 Gy animals, however rats in the 30 Gy treatment group showed stereotypic and ambulatory behavioral hyperactivity 32 weeks after irradiation. Regulatory changes in the high dose group included decreased growth rate and decreased urine osmolalities, but these measures were extremely variable among animals. Morphological results demonstrated that 30 Gy irradiated animals showed extensive necrosis primarily in the fimbria, which extended into the internal capsule, optic nerve, hippocampus, and thalamus. Hemorrhages were found in the hippocampus, thalamus, and fimbria. Defects in the blood-brain barrier also were evident by entry of intravascularly injected horseradish peroxidase into the parenchyma of the brain. Animals in the 30 Gy grafted group showed fewer behavioral changes and less brain damage than their sham grafted counterparts. Specifically, activity measures were comparable to normal levels, and a dilute urine was not found in the 30 Gy implanted rats. Morphological changes support these behavioral results since only two 30 Gy implanted rats showed necrosis.

  16. The effects of acute alcohol on motor impairments in adolescent, adult, and aged rats.

    PubMed

    Ornelas, Laura C; Novier, Adelle; Van Skike, Candice E; Diaz-Granados, Jaime L; Matthews, Douglas B

    2015-03-01

    Acute alcohol exposure has been shown to produce differential motor impairments between aged and adult rats and between adolescent and adult rats. However, the effects of acute alcohol exposure among adolescent, adult, and aged rats have yet to be systematically investigated within the same project using a dose-dependent analysis. We sought to determine the age- and dose-dependent effects of acute alcohol exposure on gross and coordinated motor performance across the rodent lifespan. Adolescent (PD 30), adult (PD 70), and aged (approximately 18 months) male Sprague-Dawley rats were tested on 3 separate motor tasks: aerial righting reflex (ARR), accelerating rotarod (RR), and loss of righting reflex (LORR). In a separate group of animals, blood ethanol concentrations (BEC) were determined at multiple time points following a 3.0 g/kg ethanol injection. Behavioral tests were conducted with a Latin square repeated-measures design in which all animals received the following doses: 1.0 g/kg or 2.0 g/kg alcohol or saline over 3 separate sessions via intraperitoneal (i.p.) injection. During testing, motor impairments were assessed on the RR 10 min post-injection and on ARR 20 min post-injection. Aged animals spent significantly less time on the RR when administered 1.0 g/kg alcohol compared to adult rats. In addition, motor performance impairments significantly increased with age after 2.0 g/kg alcohol administration. On the ARR test, aged rats were more sensitive to the effects of 1.0 g/kg and 2.0 g/kg alcohol compared to adolescents and adults. Seven days after the last testing session, animals were given 3.0 g/kg alcohol and LORR was examined. During LORR, aged animals slept longer compared to adult and adolescent rats. This effect cannot be explained solely by BEC levels in aged rats. The present study suggests that acute alcohol exposure produces greater motor impairments in older rats when compared to adolescent and adult rats and begins to establish a

  17. Testosterone differentially alters cocaine-induced ambulatory and rearing behavioral responses in adult and adolescent rats

    PubMed Central

    Minerly, AnaChristina E.; Wu, Hui Bing K.; Weierstall, Karen M.; Niyomchai, Tipyamol; Kemen, Lynne; Jenab, Shirzad; Quinones-Jenab, Vanya

    2016-01-01

    Little is known about the physiological and behavioral effects of testosterone when co-administered with cocaine during adolescence. The present study aimed to determine whether exogenous testosterone administration differentially alters psychomotor responses to cocaine in adolescent and adult male rats. To this end, intact adolescent (30-days-old) and adult (60-day-old) male Fisher rats were pretreated with vehicle (sesame oil) or testosterone (5 or 10 mg/kg) 45 minutes prior to saline or cocaine (20 mg/kg) administration. Behavioral responses were monitored 1 hour after drug treatment, and serum testosterone levels were determined. Serum testosterone levels were affected by age: saline- and cocaine-treated adults in the vehicle groups had higher serum testosterone levels than adolescents rats, but after co-administration of testosterone the adolescent rats had higher serum testosterone levels than the adults. Pretreatment with testosterone affected baseline activity in adolescent rats: 5 mg/kg of testosterone increased both rearing and ambulatory behaviors in saline-treated adolescent rats. After normalizing data to % saline, an interaction between hormone administration and cocaine-induced behavioral responses was observed; 5 mg/kg of testosterone decreased both ambulatory and rearing behaviors among adolescents whereas 10 mg/kg of testosterone decreased only rearing behaviors. Testosterone pretreatment did not alter cocaine-induced behavioral responses in adult rats. These findings suggest that adolescents are more sensitive than adults to an interaction between testosterone and cocaine, and, indirectly, suggest that androgen abuse may lessen cocaine-induced behavioral responses in younger cocaine users. PMID:19822170

  18. Unpredictable chronic stress in juvenile or adult rats has opposite effects, respectively, promoting and impairing resilience.

    PubMed

    Ricon, T; Toth, E; Leshem, M; Braun, K; Richter-Levin, G

    2012-01-01

    We evaluated the effects of early maternal deprivation (MD; age 7-14 days) alone or in combination with unpredictable chronic stress (UCS; MDUN; 28-84 days) on anxiety and learning in 90 days old adult rats. We hypothesized that exposure to both stressors (MDUN) would be more detrimental than exposure to one or neither. Unexpectedly, adult rats from the MDUN group did not differ from control animals, whereas adult MD animals exhibited impaired avoidance learning. We next investigated the effect of juvenile-onset (30-90 days) versus adult-onset (60-90 days) stress on avoidance learning in adulthood (90 days). We found that adult-onset chronic stress impaired avoidance learning and memory whereas juvenile-onset stress did not. Thus, the results again indicate that juvenile exposure to UCS induces resilience rather than impairment.

  19. Adult neurogenesis and its anatomical context in the hippocampus of three mole-rat species

    PubMed Central

    Amrein, Irmgard; Becker, Anton S.; Engler, Stefanie; Huang, Shih-hui; Müller, Julian; Slomianka, Lutz; Oosthuizen, Maria K.

    2014-01-01

    African mole-rats (family Bathyergidae) are small to medium sized, long-lived, and strictly subterranean rodents that became valuable animal models as a result of their longevity and diversity in social organization. The formation and integration of new hippocampal neurons in adult mammals (adult hippocampal neurogenesis, AHN) correlates negatively with age and positively with habitat complexity. Here we present quantitative data on AHN in wild-derived mole-rats of 1 year and older, and briefly describe its anatomical context including markers of neuronal function (calbindin and parvalbumin). Solitary Cape mole-rats (Georychus capensis), social highveld mole-rats (Cryptomys hottentotus pretoriae), and eusocial naked mole-rats (Heterocephalus glaber) were assessed. Compared to other rodents, the hippocampal formation in mole-rats is small, but shows a distinct cytoarchitecture in the dentate gyrus and CA1. Distributions of the calcium-binding proteins differ from those seen in rodents; e.g., calbindin in CA3 of naked mole-rats distributes similar to the pattern seen in early primate development, and calbindin staining extends into the stratum lacunosum-moleculare of Cape mole-rats. Proliferating cells and young neurons are found in low numbers in the hippocampus of all three mole-rat species. Resident granule cell numbers are low as well. Proliferating cells expressed as a percentage of resident granule cells are in the range of other rodents, while the percentage of young neurons is lower than that observed in surface dwelling rodents. Between mole-rat species, we observed no difference in the percentage of proliferating cells. The percentages of young neurons are high in social highveld and naked mole-rats, and low in solitary Cape mole-rats. The findings support that proliferation is regulated independently of average life expectancy and habitat. Instead, neuronal differentiation reflects species-specific demands, which appear lower in subterranean rodents. PMID

  20. Sexually dimorphic effects of neonatal immune system activation with lipopolysaccharide on the behavioural response to a homotypic adult immune challenge.

    PubMed

    Tenk, Christine M; Kavaliers, Martin; Ossenkopp, Klaus-Peter

    2008-01-01

    Research has shown that acute immune activation during the early postnatal period with the Gram-negative endotoxin, lipopolysaccharide (LPS), alters a variety of physiological and behavioural processes in the adult animal. For example, neonatal LPS exposure affects disease susceptibility later in life, though these effects appear to be modulated by time of exposure, sex, and immune stimulus. The current study examined sex differences in the effect of neonatal LPS treatment on the locomotor activity response to adult LPS administration. Male and female Long-Evans rats were treated systemically with either LPS (50 microg/kg) or saline (0.9%) on postnatal days 3 and 5. Later in adulthood (postnatal day 92), all animals were subjected to an adult LPS challenge and were injected (i.p.) with 200 microg/kg LPS. Two hours after injection, animals were placed in a non-novel open-field and locomotor activity was assessed for 30 min. Body weights were determined both at the time of injection and 24h later to examine LPS-induced weight loss. Adult males treated neonatally with LPS exhibited significantly less horizontal and vertical activity in response to the LPS challenge relative to males treated neonatally with saline. This effect was not observed in females. Thus, the current study provides important evidence of sexual dimorphism in the long-term effects of neonatal LPS exposure on the responses to an adult homotypic immune challenge in rats. These findings have potential clinical significance given that neonatal exposure to pathogens is a fairly common occurrence and Gram-negative bacteria are a common cause of neonatal bacterial infections.

  1. Post-training re-exposure to fear conditioned stimuli enhances memory consolidation and biases rats toward the use of dorsolateral striatum-dependent response learning.

    PubMed

    Leong, Kah-Chung; Goodman, Jarid; Packard, Mark G

    2015-09-15

    In a dual-solution task that can be acquired using either hippocampus-dependent "place" or dorsolateral striatum-dependent "response" learning, emotional arousal induced by unconditioned stimuli (e.g. anxiogenic drug injections or predator odor exposure) biases rats toward response learning. In the present experiments emotionally-arousing conditioned stimuli were used to modulate the relative use of multiple memory systems. In Experiment 1, adult male Long-Evans rats initially received three standard fear-conditioning trials in which a tone (2 kHz, 75 dB) was paired with a brief electrical shock (1 mA, 2s). On day 2, the rats were trained in a dual-solution plus-maze task to swim from the same start arm (South) to a hidden escape platform always located in the same goal arm (East). Immediately following training, rats received post-training re-exposure to the fear-conditioned stimuli (i.e. tone and context) without shock. On day 3, the relative use of place or response learning was assessed on a probe trial in which rats were started from the opposite start arm (North). Post-training re-exposure to fear-conditioned stimuli produced preferential use of a response strategy. In Experiment 2, different rats received fear conditioning and were then trained in a single-solution task that required the use of response learning. Immediately following training, rats received post-training re-exposure to the fear-conditioned stimuli without shock. Re-exposure to fear-conditioned stimuli enhanced memory consolidation in the response learning task. Thus, re-exposure to fear-conditioned stimuli biases rats toward the use of dorsolateral striatum-dependent response learning and enhances memory consolidation of response learning.

  2. Chronic high fat feeding increases anxiety-like behaviour and reduces transcript abundance of glucocorticoid signalling genes in the hippocampus of female rats.

    PubMed

    Sivanathan, Shathveekan; Thavartnam, Kabriya; Arif, Shahneen; Elegino, Trisha; McGowan, Patrick O

    2015-06-01

    The consumption of diets high in saturated fats and obesity have been associated with impaired physical and mental health. Previous studies indicate that chronic high fat diet consumption leads to systemic inflammation in humans and non-human animal models. Studies in non-human animals suggest that altered physiological responses to stress are also a consequence of high fat diet consumption. Glucocorticoid signalling mechanisms may link immune and stress-related pathways in the brain, and were shown to be significantly altered in the brains of female rat offspring of mothers exposed to chronic high fat diet during pregnancy and lactation. For adult females, the consequence of chronic high fat diet consumption on these signalling pathways and their relationship to stress-related behaviour is not known. In this study, we examined the effects of chronic consumption of a high fat diet compared to a low fat control diet among adult female Long Evans rats. We found significant differences in weight gain, caloric intake, anxiety-related behaviours, and glucocorticoid-related gene expression over a 10-week exposure period. As expected, rats in the high fat diet group gained the most weight and consumed the greatest number of calories. Rats in the high fat diet group showed significantly greater levels of anxiety-related behaviour in the Light Dark and Open Field tasks compared to rats in the low fat diet group. Rats consuming high fat diet also exhibited reduced transcript abundance in the hippocampus of stress-related mineralocorticoid receptor and glucocorticoid receptor genes, as well as nuclear factor kappa beta gene expression, implicated in inflammatory processes. Together, these data indicate that chronic high fat diet consumption may increase anxiety-like behaviour at least in part via alterations in glucocorticoid signalling mechanisms in limbic brain regions.

  3. Ethanol facilitation of short-term memory in adult rats with a disturbed circadian cycle.

    PubMed

    Mikolajczak, P; Okulicz-Kozaryn, I; Nowaczyk, M; Kaminska, E

    2001-01-01

    The aim of this study was to evaluate the effect of 3-month ethanol treatment on olfactory social memory test performance using two inter-exposure intervals [30 min: short-term recognition (STR); or 120 min: long-term recognition (LTR)] in adult rats with a disturbed circadian cycle (DCC). Ethanol treatment both in ethanol-preferring and -non-preferring groups improved the STR task compared to control rats. However, LTR procedure triggered the opposite tendency. Moreover, no differences between control rats with DCC and those with normal diurnal rhythm in STR and LTR paradigms were observed. Our results suggest that, under some conditions, alcohol facilitates short-term memory in adult rats. PMID:11468127

  4. Adaptations of young adult rat cortical bone to 14 days of spaceflight

    NASA Technical Reports Server (NTRS)

    Vailas, A. C.; Vanderby, R., Jr.; Martinez, D. A.; Ashman, R. B.; Ulm, M. J.; Grindeland, R. E.; Durnova, G. N.; Kaplanskii, A.

    1992-01-01

    To determine whether mature humeral cortical bone would be modified significantly by an acute exposure to weightlessness, adult rats (110 days old) were subjected to 14 days of microgravity on the COSMOS 2044 biosatellite. There were no significant changes in peak force, stiffness, energy to failure, and displacement at failure in the flight rats compared with ground-based controls. Concentrations and contents of hydroxyproline, calcium, and mature stable hydroxylysylpyridinoline and lysylpyridinoline collagen cross-links remained unchanged after spaceflight. Bone lengths, cortical and endosteal areas, and regionl thicknesses showed no significant differences between flight animals and ground controls. The findings suggest that responsiveness of cortical bone to microgravity is less pronounced in adult rats than in previous spaceflight experiments in which young growing animals were used. It is hypothesized that 14 days of spaceflight may not be sufficient to impact the biochemical and biomechanical properties of cortical bone in the mature rat skeleton.

  5. Regeneration of central cholinergic neurones in the adult rat brain.

    PubMed

    Svendgaard, N A; Björklund, A; Stenevi, U

    1976-01-30

    The regrowth of lesioned central acetylcholinesterase (AChE)-positive axons in the adult rat was studied in irides implanted to two different brain sites: in the caudal diencephalon and hippocampus, and in the hippocampal fimbria. At both implantation sites the cholinergic septo-hippocampal pathways were transected. At 2-4 weeks after lesion, newly formed, probably sprouting fibres could be followed in abundance from the lesioned proximal axon stumps into the iris transplant. Growth of newly formed AChE-positive fibres into the transplant was also observed from lesioned axons in the anterior thalamus, and to a minor extent also from the dorsal and ventral tegmental AChE-positive pathways and the habenulo-interpeduncular tract. The regrowth process of the sprouting AChE-positive, presumed cholinergic fibres into the iris target was studied in further detail in whole-mount preparations of the transplants. For this purpose the irides were removed from the brain, unfolded, spread out on microscope slides, and then stained for AChE. During the first 2-4 weeks after transplantation the sprouting central fibres grew out over large areas of the iris. The new fibres branched profusely into a terminal plexus that covered maximally about half of the iris surface, and in some areas the patterning of the regenerated central fibres mimicked closely that of the normal autonomic cholinergic innervation of the iris. In one series of experiments the AChE-staining was combined with fluorescence histochemical visualization of regenerated adrenergic fibres in the same specimens. In many areas there was a striking congruence in the distributional patterns of the regenerated central cholinergic and adrenergic fibres in the transplant. This indicates that - as in the normal iris - the sprouting cholinergic axons (primarily originating in the lesioned septo-hippocampal pathways) and adrenergic axons (primarily originating in the lesioned axons of the locus neurones) regenerate together

  6. Dose related effects of nicotine on oxidative injury in young, adult and old rats.

    PubMed

    Jain, Anshu; Flora, S J S

    2012-03-01

    Nicotine affects a variety of cellular process ranging from induction of gene expression to secretion of hormones and modulation of enzymatic activities. The objective of the present study was to study the dose dependent toxicity of nicotine on the oxidative stress in young, adult and old rats which were administered 0.75, 3 and 6 mg kg(-1) nicotine as nicotine hydrogen tartarate intraperitoneally for a period of seven days. No changes were observed in blood catalase (CAT) activity and level of blood reactive oxygen species (ROS) in any of the age group at the lowest dose of nicotine. However, at the highest dose (6 mg kg(-1) nicotine) ROS level increased significantly from 1.17 to 1.41 microM ml(-1) in young rats and from 1.13 to 1.40 microM ml(-1) in old rats. However, no change was observed in blood ROS levels of adult rats. Administration of 3 mg kg(-1) nicotine resulted in an increase in level of reduced glutathione (GSH) in rats of all the age groups. The young animals were the most sensitive as a dose of 6 mg kg(-1) resulted in decline in the levels of reduced GSH to 0.89 mg ml(-1) as compared to normal control (1.03 mg ml(-1)). The antioxidant enzymes SOD and CAT were sensitive to a dose of 6 mg kg(-1) as it resulted in decline of the enzymatic activity in all age group animals. Also, administration of nicotine at a lower dose of 3 mg kg(-1) inhibited SOD activity from 1.48 to 1.20 units min(-1) mg(-1) protein in old rats. Catalase activity showed a similar trend at a dose of 3 mg kg(-1). Administration of nicotine also increased the blood lipid peroxidation levels at all three doses in young and old rats dose dependently. Nicotine exposure also increased ROS in brain at the doses of 3 and 6 mg kg(-1) in all the three age groups. Brain GSH decreased significantly at high dose of nicotine (6 mg kg(-1) b.wt.) in adult rats (4.27 mg g(-1)) and old rats (3.68 mg g(-1)) but in young rats level increased to 4.40 mg g(-1) at the lower dose (0.75 mg kg nicotine

  7. Methylphenidate treatment increases Na(+), K (+)-ATPase activity in the cerebrum of young and adult rats.

    PubMed

    Scherer, Emilene B S; Matté, Cristiane; Ferreira, Andréa G K; Gomes, Karin M; Comim, Clarissa M; Mattos, Cristiane; Quevedo, João; Streck, Emilio L; Wyse, Angela T S

    2009-12-01

    Methylphenidate is a central nervous system stimulant used for the treatment of attention-deficit hyperactivity disorder. Na(+), K(+)-ATPase is a membrane-bound enzyme necessary to maintain neuronal excitability. Considering that methylphenidate effects on central nervous system metabolism are poorly known and that Na(+), K(+)-ATPase is essential to normal brain function, the purpose of this study was to evaluate the effect of this drug on Na(+), K(+)-ATPase activity in the cerebrum of young and adult rats. For acute administration, a single injection of methylphenidate (1.0, 2.0, or 10.0 mg/Kg) or saline was given to rats on postnatal day 25 or postnatal day 60, in the young and adult groups, respectively. For chronic administration, methylphenidate (1.0, 2.0, or 10.0 mg/Kg) or saline injections were given to young rats starting at postnatal day 25 once daily for 28 days. In adult rats, the same regimen was performed starting at postnatal day 60. Our results showed that acute methylphenidate administration increased Na(+), K(+)-ATPase activity in hippocampus, prefrontal cortex, and striatum of young and adult rats. In young rats, chronic administration of methylphenidate also enhanced Na(+), K(+)-ATPase activity in hippocampus and prefrontal cortex, but not in striatum. When tested in adult rats, Na(+), K(+)-ATPase activity was increased in all cerebral structures studied. The present findings suggest that increased Na(+), K(+)-ATPase activity may be associated with neuronal excitability caused by methylphenidate.

  8. Perinatal exposure to diethylstilbestrol alters the functional differentiation of the adult rat uterus.

    PubMed

    Bosquiazzo, Verónica L; Vigezzi, Lucía; Muñoz-de-Toro, Mónica; Luque, Enrique H

    2013-11-01

    The exposure to endocrine disrupters and female reproductive tract disorders has not been totally clarified. The present study assessed the long-term effect of perinatal (gestation+lactation) exposure to diethylstilbestrol (DES) on the rat uterus and the effect of estrogen replacement therapy. DES (5μg/kg bw/day) was administered in the drinking water from gestational day 9 until weaning and we studied the uterus of young adult (PND90) and adult (PND360) females. To investigate whether perinatal exposure to DES modified the uterine response to a long-lasting estrogen treatment, 12-month-old rats exposed to DES were ovariectomized and treated with 17β-estradiol for 3 months (PND460). In young adult rats (PND90), the DES treatment decreased both the proliferation of glandular epithelial cells and the percentage of glandular perimeter occupied by α-smooth muscle actin-positive cells. The other tissue compartments remained unchanged. Cell apoptosis was not altered in DES-exposed females. In control adult rats (PND360), there were some morphologically abnormal uterine glands. In adult rats exposed to DES, the incidence of glands with cellular anomalies increased. In response to estrogens (PND460), the incidence of cystic glands increased in the DES group. We observed glands with daughter glands and conglomerates of glands only on PND460 and in response to estrogen replacement therapy, independently of DES exposure. The p63 isoforms were expressed without changes on PND460. Estrogen receptors α and β showed no changes, while the progesterone receptor decreased in the subepithelial stroma of DES-exposed animals with estrogen treatment. The long-lasting effects of perinatal exposure to DES included the induction of abnormalities in uterine tissues of aged female rats and an altered response of the adult uterus to estradiol.

  9. Comparison of catalase immunoreactivity in the hippocampus between young, adult and aged mice and rats

    PubMed Central

    AHN, JI HYEON; CHEN, BAI HUI; SHIN, BICH-NA; LEE, TAE-KYEONG; CHO, JEONG HWI; KIM, IN HYE; PARK, JOON HA; LEE, JAE-CHUL; TAE, HYUN-JIN; LEE, CHOONG-HYUN; WON, MOO-HO; LEE, YUN LYUL; CHOI, SOO YOUNG; HONG, SEONGKWEON

    2016-01-01

    Catalase (CAT) is an important antioxidant enzyme and is crucial in modulating synaptic plasticity in the brain. In this study, CAT expression as well as neuronal distribution was compared in the hippocampus among young, adult and aged mice and rats. Male ICR mice and Sprague Dawley rats were used at postnatal month (PM) 1, PM 6 and PM 24 as the young, adult and aged groups, respectively (n=14/group). CAT expression was examined by immunohistochemistry and western blot analysis. In addition, neuronal distribution was examined by NeuN immunohistochemistry. In the present study, the mean number of NeuN-immunoreactive neurons was marginally decreased in mouse and rat hippocampi during aging, although this change was not identified to be significantly different. However, CAT immunoreactivity was significantly increased in pyramidal and granule neurons in the adult mouse and rat hippocampi and was significantly decreased in the aged mouse and rat hippocampi compared with that in the young animals. CAT protein levels in the hippocampus were also lowest in the aged mouse and rat hippocampus. These results indicate that CAT expression is significantly decreased in the hippocampi of aged animals and decreased CAT expression may be closely associated with aging. PMID:27221506

  10. Vitamin A Kinetics in Neonatal Rats vs. Adult Rats: Comparisons from Model-Based Compartmental Analysis12

    PubMed Central

    Tan, Libo; Green, Michael H; Ross, A Catharine

    2015-01-01

    A critical role for vitamin A (VA) in development is well established, but still relatively little is known about whole-body VA metabolism in early postnatal life. Recently, methods of mathematical modeling have begun to shed light on retinol kinetics in the postnatal growth period and on the effect of retinoid supplementation on retinol kinetics. Comparison of kinetic parameters from tracer studies in neonatal rats with those previously determined in models of VA metabolism in the adult suggests both similarities and differences in the relative transfer rates of plasma retinol to extrahepatic tissues, resulting in similarities and differences in kinetic parameters and inferences about physiologic processes. Similarities between neonatal and adult models include the capacity for efficient digestion and absorption of VA; characteristics of a high-response system; extensive retinol recycling among liver, plasma, and extrahepatic tissues; and comparable VA disposal rates. Differences between neonatal and adult models include that, in neonates, retinol turnover is faster and retinol recycling is much more extensive; there is a greater role for extrahepatic tissues in the uptake of chylomicron VA; and the intestine plays an important role in chylomicron VA uptake, especially in neonatal rats treated with a supplement containing VA. In summary, retinol kinetic modeling in the neonatal rat has provided a first view of whole-body VA metabolism in this age group and suggests that VA kinetics in neonatal rats differs in many ways from that in adults, perhaps reflecting an adaption to the lower VA concentration found in neonates compared with adults. PMID:25540407

  11. Acute postnatal exposure to the pentaBDE commercial mixture DE-71 at 5 or 15 mg/kg/day does not produce learning or attention deficits in rats.

    PubMed

    Driscoll, Lori L; Kaplan, Joshua; Bucuvalas, Eleni; Allen, Hunter; Kraut, Joshua; Fitzpatrick, Jesse

    2012-01-01

    Polybrominated diphenyl ethers (PBDEs), flame retardant chemicals added to polymer products, have become ubiquitous in the environment, and they are bioaccumulating in humans and wildlife. Therefore, understanding their biological effects is important for public health. We have previously observed learning deficits in rats exposed to DE-71, a commercial PBDE mixture consisting primarily of pentabrominated diphenyl ethers, at a dose of 30 mg/kg/day from postnatal day (PND) 6 to 12. The purpose of the current study was to determine if this effect could be seen with lower doses of DE-71. Long-Evans rats were administered daily oral doses of corn oil alone or DE-71, 5 or 15 mg/kg/day, dissolved in corn oil, from PND 6 to 12. As young adults, the rats were administered a series of five-choice visual learning and attention tasks. No effects of DE-71 were found on learning, attention, or inhibitory control. Given that developmental DE-71 exposure at similar doses and for shorter time periods has been shown in other laboratories to affect locomotion and hyperactivity, the current results suggest that cognitive functions may not be as sensitive as neuromotor functions to the effects of acute DE-71 exposure.

  12. Simultaneous study of haemodynamic, metabolic and behavioural sequelae in a model of cerebral ischaemia in aged rats: effects of nicergoline.

    PubMed

    Le Poncin-Lafitte, M; Grosdemouge, C; Duterte, D; Rapin, J R

    1984-01-01

    Unilateral cerebral ischaemia was induced in 18-month-old Long-Evans rats by injection of 2,000 labelled microspheres (phi 50 microns) into the carotid blood stream. This results in an ipsilateral decrease in cerebral blood flow, development of severe oedema and modifications of glucose uptake and consumption. Furthermore, this ischaemia led to a deterioration of the avoidance response in conditioned animals. All these disturbances, including the cerebral oedema, diminished with nicergoline pretreatment. PMID:6706123

  13. Prenatal choline availability alters the context sensitivity of Pavlovian conditioning in adult rats.

    PubMed

    Lamoureux, Jeffrey A; Meck, Warren H; Williams, Christina L

    2008-12-01

    The effects of prenatal choline availability on Pavlovian conditioning were assessed in adult male rats (3-4 mo). Neither supplementation nor deprivation of prenatal choline affected the acquisition and extinction of simple Pavlovian conditioned excitation, or the acquisition and retardation of conditioned inhibition. However, prenatal choline availability significantly altered the contextual control of these learned behaviors. Both control and choline-deprived rats exhibited context specificity of conditioned excitation as exhibited by a loss in responding when tested in an alternate context after conditioning; in contrast, choline-supplemented rats showed no such effect. When switched to a different context following extinction, however, both choline-supplemented and control rats showed substantial contextual control of responding, whereas choline-deficient rats did not. These data support the view that configural associations that rely on hippocampal function are selectively sensitive to prenatal manipulations of dietary choline during prenatal development.

  14. Prenatal choline availability alters the context sensitivity of Pavlovian conditioning in adult rats

    PubMed Central

    Lamoureux, Jeffrey A.; Meck, Warren H.; Williams, Christina L.

    2008-01-01

    The effects of prenatal choline availability on Pavlovian conditioning were assessed in adult male rats (3–4 mo). Neither supplementation nor deprivation of prenatal choline affected the acquisition and extinction of simple Pavlovian conditioned excitation, or the acquisition and retardation of conditioned inhibition. However, prenatal choline availability significantly altered the contextual control of these learned behaviors. Both control and choline-deprived rats exhibited context specificity of conditioned excitation as exhibited by a loss in responding when tested in an alternate context after conditioning; in contrast, choline-supplemented rats showed no such effect. When switched to a different context following extinction, however, both choline-supplemented and control rats showed substantial contextual control of responding, whereas choline-deficient rats did not. These data support the view that configural associations that rely on hippocampal function are selectively sensitive to prenatal manipulations of dietary choline during prenatal development. PMID:19050158

  15. Histological effects of chronic consumption of soda pop drinks on kidney of adult Wister rats

    PubMed Central

    Adjene, Josiah Obaghwarhievwo; Ezeoke, Joseph Chigozie; Nwose, Ezekiel Uba

    2010-01-01

    Background: Health concerns over soda pop drinks have been severally report. However, histological perspectives are not very common. Aim: The objective of this study is to investigate histological effect of chronic consumption of soda pop drinks on the kidney of adult Wistar rats. Materials and methods: The rats of both sexes (n = 24), with average weight of 200g were randomly assigned into two treatment (A & B) (n=16) and Control (c) (n=8) groups. The rats in the treatment group (A) received a brand of soda pop drink on a daily basis for thirty days. The rats in treatment group (B) received another brand of soda drink, while the control group (C) received equal amount of water for the same period. The rats were given the drinks as well as feeds liberally for thirty days, and sacrificed by cervical dislocation on the thirty-first day of the experiment. The kidney was carefully dissected out and quickly fixed in 10% formal saline for histological study. Results: The findings indicate that rats in the treated groups (A&B) showed some varying degree of distortion and disruption of the renal structure. There are observable diffuse signs of glomerulonephritis with some congestion and tubular necrosis as compared to the control group. Conclusion: Chronic consumption of soda pop drinks may affect the microanatomy of the kidney of adult Wistar rats. Further study aimed at corroborating these observations in humans is warranted. PMID:22574291

  16. The Effects of Inflammatory Tooth Pain on Anxiety in Adult Male Rats

    PubMed Central

    Raoof, Maryam; Ebrahimnejad, Hamed; Abbasnejad, Mehdi; Amirkhosravi, Ladan; Raoof, Ramin; Esmaeili Mahani, Saeed; Ramazani, Mohsen; Shokouhinejad, Noushin; Khoshkhounejad, Mehrfam

    2016-01-01

    Introduction: This study aimed to examine the effects of induced inflammatory tooth pain on anxiety level in adult male rats. Methods: The mandibular incisors of 56 adult male rats were cut off and prefabricated crowns were fixed on the teeth. Formalin and capsaicin were injected intradentally to induce inflammatory tooth pain. Diazepam treated group received diazepam 30 minutes before intradental injection. The anxiety-related behavior was evaluated with elevated plus maze test. Results: Intradental application of chemical noxious stimuli, capsaicin and formalin, significantly affected nociceptive behaviors (P<0.001). Capsaicin (P<0.001) and formalin (P<0.01) significantly increased the anxiety levels in rats by decrease in the duration of time spent in open arm and increase in the duration of time spent in closed arm. Rats that received capsaicin made fewer open arm entries compared to the control animals (P<0.05). Capsaicin (P<0.001) and formalin (P<0.01) treated rats showed more stretch attend postures compared to the control and sham operated animals. In diazepampretreated rats, capsaicin induced algesic effect was prevented (P<0.001). Conclusion: Inflammatory pulpal pain has anxiogenic effect on rats, whereas diazepam premedication showed both anxiolytic and pain reducing effects. PMID:27563419

  17. Different adaptation of the motor activity rhythm to chronic phase shifts between adolescent and adult rats.

    PubMed

    Albert, Nerea; da Silva, Crhistiane; Díez-Noguera, Antoni; Cambras, Trinitat

    2013-09-01

    Chronic phase shifts is a common feature in modern societies, which may induce sleep alterations and other health problems. The effects of phase shift on the circadian rhythms have been described to be more pronounced in old than in young animals. However, few works address the effects of chronic phase shifts during adolescence. Here we tested the development of the motor activity circadian rhythm of young rats under chronic phase shifts, which consisted on 6-h advances (A), 6h delays (D) or 6h advances and delays alternated every 5 days (AD) during the first 60 days after weaning. Moreover, the rhythmic pattern was compared to that of adult rats under the same lighting conditions. Results indicate that adolescent rats, independently on the lighting environment, developed a clear circadian rhythm, whose amplitude increased the first 50 days after weaning and showed a more stable circadian rhythm than adults under the same lighting conditions. In the case of A and AD groups, circadian disruption was observed only in adult rats. In all groups, the offset of activity correlated with light pattern better than the onset, and this correlation was always higher in the case of the rhythm of the pubertal rats. When AD groups were transferred to constant darkness, the group submitted to this condition during adolescence showed shorter period than that submitted in their adulthood. In conclusion, differently from adult rats, adolescent rats submitted to chronic phase shifts did not show circadian disruption and developed a single circadian rhythm, suggesting permanent changes in the circadian system.

  18. Different adaptation of the motor activity rhythm to chronic phase shifts between adolescent and adult rats.

    PubMed

    Albert, Nerea; da Silva, Crhistiane; Díez-Noguera, Antoni; Cambras, Trinitat

    2013-09-01

    Chronic phase shifts is a common feature in modern societies, which may induce sleep alterations and other health problems. The effects of phase shift on the circadian rhythms have been described to be more pronounced in old than in young animals. However, few works address the effects of chronic phase shifts during adolescence. Here we tested the development of the motor activity circadian rhythm of young rats under chronic phase shifts, which consisted on 6-h advances (A), 6h delays (D) or 6h advances and delays alternated every 5 days (AD) during the first 60 days after weaning. Moreover, the rhythmic pattern was compared to that of adult rats under the same lighting conditions. Results indicate that adolescent rats, independently on the lighting environment, developed a clear circadian rhythm, whose amplitude increased the first 50 days after weaning and showed a more stable circadian rhythm than adults under the same lighting conditions. In the case of A and AD groups, circadian disruption was observed only in adult rats. In all groups, the offset of activity correlated with light pattern better than the onset, and this correlation was always higher in the case of the rhythm of the pubertal rats. When AD groups were transferred to constant darkness, the group submitted to this condition during adolescence showed shorter period than that submitted in their adulthood. In conclusion, differently from adult rats, adolescent rats submitted to chronic phase shifts did not show circadian disruption and developed a single circadian rhythm, suggesting permanent changes in the circadian system. PMID:23792134

  19. Pharmacokinetics of bisphenol A in neonatal and adult Sprague-Dawley rats

    SciTech Connect

    Doerge, Daniel R.; Twaddle, Nathan C.; Vanlandingham, Michelle; Fisher, Jeffrey W.

    2010-09-01

    Bisphenol A (BPA) is an important industrial chemical used in the manufacture of polycarbonate plastic products and epoxy resin-based food can liners. The presence of BPA in urine of > 90% of Americans aged 6-60 suggests ubiquitous and frequent exposure. The current study used LC/MS/MS to measure serum pharmacokinetics of aglycone (active) and conjugated (inactive) BPA in adult and neonatal Sprague-Dawley rats by oral and injection routes. Deuterated BPA was used to avoid issues of background contamination. Linear pharmacokinetics were observed in adult rats treated orally in the range of 0-200 {mu}g/kg bw. Evidence for enterohepatic recirculation of conjugated, but not aglycone, BPA was observed in adult rats. Significant inverse relationships were observed between postnatal age and measures of internal exposures to aglycone BPA and its elimination. In neonatal rats treated orally, internal exposures to aglycone BPA were substantially lower than from subcutaneous injection. The results reinforce the critical role for first-pass Phase II metabolism of BPA in gut and liver after oral exposure that attenuates internal exposure to the aglycone form in rats of all ages. The internal exposures to aglycone BPA observed in adult and neonatal rats following a single oral dose of 100 {mu}g/kg bw are inconsistent with effects mediated by classical estrogen receptors based on binding affinities. However, an impact on alternative estrogen signaling pathways that have higher receptor affinity cannot be excluded in neonatal rats. These findings emphasize the importance of matching aglycone BPA internal dosimetry with receptor affinities in experimental animal studies reporting toxicity.

  20. Thyroxine binding to serum thyronine-binding globulin in thyroidectomized adult and normal neonatal rats

    SciTech Connect

    Young, R.A.; Meyers, B.; Alex, S.; Fang, S.L.; Braverman, L.E.

    1988-05-01

    The amount of tracer (125I)T4 bound to serum thyronine-binding globulin (TBG) was measured by polyacrylamide gel electrophoresis in adult thyroidectomized (TX) rats and normal 1-day to 4-week-old rat puts. Thyroidectomy was associated with the appearance of significant amounts of (125I)T4 binding to serum TBG in lean rats, but not in obese Zucker rats. Treatment of the TX rats in vivo with replacement doses of T4 prevented this increase in TBG binding, but enrichment of serum from TX rats with T4 did not. Significant amounts of tracer (125I)T4 binding to TBG was present in serum from 1- to 3-week-old normal rat pups, but not in 1-day- or 4-week-old pups. There were significantly higher levels of TBG binding of (125I)T4 in serum from 2-week-old rat pups raised in litters of 16 pups compared to those raised in litters of 4 pups. All manipulations that result in the appearance of TBG in rat serum also result in either weight loss or a slowing in the rate of growth, suggesting that the appearance of TBG in rat serum has a nutritional component. This possibility is further supported by the observations that increases in TBG binding of (125I)T4 are not found in obese Zucker rats fed a low protein-high carbohydrate diet for 14 days or fasted for 7 days, or after thyroidectomy, perhaps owing to the large stores of fuel in the obese rat.

  1. Zinc supplementation decreases hepatic copper accumulation in LEC rat: a model of Wilson's disease.

    PubMed

    Gonzalez, Blanca P Esparza; Niño Fong, Rodolfo; Gibson, Candace J; Fuentealba, I Carmen; Cherian, M George

    2005-01-01

    The effect of dietary zinc (Zn) supplementation on copper (Cu)-induced liver damage was investigated in Long-Evans Cinnamon rats (LEC), a model for Wilson's disease (WD). Four-week-old LEC (N=64) and control Long-Evans (LE) (N=32) female rats were divided into two groups; one group was fed with a Zn-supplemented diet (group I) and the other was given a normal rodent diet (group II). LEC rats were killed at 6, 8, 10, 12, 18, and 20 wk of age; the LE control rats were killed at 6, 12, 18, and 20 wk of age. Cu concentration in the liver was reduced in LEC rats fed the Zn-supplemented diet compared with LEC rats on the normal diet between 6 and 18 wk of age. Metallothionein (MT) concentration in the livers of LEC rats in group I increased between 12 and 20 wk of age, whereas hepatic MT concentration in LEC rats from group II decreased after 12 wk. Hepatocyte apoptosis, as determined by TUNEL, was reduced in Zn-supplemented LEC rats at all ages. Cholangiocellular carcinoma was observed only in LEC rats in group II at wk 20. These results suggest that Zn supplementation can reduce hepatic Cu concentration and delay the onset of clinical and pathological changes of Cu toxicity in LEC rats. Although the actual mechanism of protection is unknown, it could be explained by sequestration of dietary Cu by intestinal MT, induced by high dietary Zn content.

  2. Reinstatement of cocaine seeking induced by drugs, cues, and stress in adolescent and adult rats

    PubMed Central

    Carroll, Marilyn E.

    2010-01-01

    Rationale In human and animal studies, adolescence marks a period of increased vulnerability to the initiation and subsequent abuse of drugs. Adolescents may be especially vulnerable to relapse, and a critical aspect of drug abuse is that it is a chronically relapsing disorder. However, little is known of how vulnerability factors such as adolescence are related to conditions that induce relapse, triggered by the drug itself, drug-associated cues, or stress. Objective The purpose of this study was to compare adolescent and adult rats on drug-, cue-, and stress-induced reinstatement of cocaine-seeking behavior. Methods On postnatal days 23 (adolescents) and 90 (adults), rats were implanted with intravenous catheters and trained to lever press for i.v. infusions of cocaine (0.4 mg/kg) during two daily 2-h sessions. The rats then self-administered i.v. cocaine for ten additional sessions. Subsequently, visual and auditory stimuli that signaled drug delivery were unplugged, and rats were allowed to extinguish lever pressing for 20 sessions. Rats were then tested on cocaine-, cue-, and yohimbine (stress)-induced cocaine seeking using a within-subject multicomponent reinstatement procedure. Results Results indicated that adolescents had heightened cocaine seeking during maintenance and extinction compared to adults. During reinstatement, adolescents (vs adults) responded more following cocaine- and yohimbine injections, while adults (vs adolescents) showed greater responding following presentations of drug-associated cues. Conclusion These results demonstrated that adolescents and adults differed across several measures of drug-seeking behavior, and adolescents may be especially vulnerable to relapse precipitated by drugs and stress. PMID:19953228

  3. Regulatory Mechanism of Muscle Disuse Atrophy in Adult Rats

    NASA Technical Reports Server (NTRS)

    1993-01-01

    During the last phase of NAG 2-386 we completed three studies. The effects of 14 days of weightlessness; the vastus medialis (VM) from flight rats in COSMOS 2044 was compared with the VM from tail suspended rats and other controls. The type I and II fibers in the mixed fiber portion of the VM were significantly reduced in flight rats and capillary densities paralleled the fiber density changes. The results of this project compared favorably with those in the extensor digitorum longus following seven days of flight in SL 3. The cardiovascular projects focused on the blood pressure changes in head down tilted rats (HDT) and non-head down tilted (N-HDT) rats. Blood pressures (MAP, SP and DP) were significantly elevated through seven days of HDT and rapidly returned to control levels within one day after removal from the HDT position. The N-HDT showed some slight rise in blood pressure but these were not as great and they were not as rapid. The HDT rats were characterized as exhibiting transient hypertension. These results led to some of the microvascular and vascular graduate student projects of Dr. Bernhard Stepke. Also our results refute or, at least, do not agree with previous reports from other laboratories. Each animal, in our blood pressure projects, served as its own control thereby providing more accurate results. Also, our experiments focused on recovery studies which can, in and of themselves, provide guidelines for flight experiments concerned with blood pressure changes. Another experiment was conducted to examine the role of testicular atrophy in whole body suspended (WBS) and tail suspended (TS) rats. We worked in conjunction with Dr. D.R. Deaver's laboratory at Pennsylvania State University and Dr. R. P. Amann at Colorado State University. In the TS rats the testes are retracted into the abdominal cavity, unless a ligature is placed to maintain them in the external scrotal sac. The cryptorchid condition in TS rats results in atrophy of the testes and

  4. Nickel nanoparticles exposure and reproductive toxicity in healthy adult rats.

    PubMed

    Kong, Lu; Tang, Meng; Zhang, Ting; Wang, Dayong; Hu, Ke; Lu, Weiqi; Wei, Chao; Liang, Geyu; Pu, Yuepu

    2014-01-01

    Nickel is associated with reproductive toxicity. However, the reproductive toxicity of nickel nanoparticles (Ni NPs) is unclear. Our goal was to determine the association between nickel nanoparticle exposure and reproductive toxicity. According to the one-generation reproductive toxicity standard, rats were exposed to nickel nanoparticles by gavage and we selected indicators including sex hormone levels, sperm motility, histopathology, and reproductive outcome etc. Experimental results showed nickel nanoparticles increased follicle stimulating hormone (FSH) and luteinizing hormone (LH), and lowered etradiol (E2) serum levels at a dose of 15 and 45 mg/kg in female rats. Ovarian lymphocytosis, vascular dilatation and congestion, inflammatory cell infiltration, and increase in apoptotic cells were found in ovary tissues in exposure groups. For male rats, the weights decreased gradually, the ratio of epididymis weight over body weight increased, the motility of rat sperm changed, and the levels of FSH and testosterone (T) diminished. Pathological results showed the shedding of epithelial cells of raw seminiferous tubule, disordered arrangement of cells in the tube, and the appearance of cell apoptosis and death in the exposure group. At the same time, Ni NPs resulted in a change of the reproductive index and the offspring development of rats. Further research is needed to elucidate exposure to human populations and mechanism of actions. PMID:25407529

  5. Nickel Nanoparticles Exposure and Reproductive Toxicity in Healthy Adult Rats

    PubMed Central

    Kong, Lu; Tang, Meng; Zhang, Ting; Wang, Dayong; Hu, Ke; Lu, Weiqi; Wei, Chao; Liang, Geyu; Pu, Yuepu

    2014-01-01

    Nickel is associated with reproductive toxicity. However, the reproductive toxicity of nickel nanoparticles (Ni NPs) is unclear. Our goal was to determine the association between nickel nanoparticle exposure and reproductive toxicity. According to the one-generation reproductive toxicity standard, rats were exposed to nickel nanoparticles by gavage and we selected indicators including sex hormone levels, sperm motility, histopathology, and reproductive outcome etc. Experimental results showed nickel nanoparticles increased follicle stimulating hormone (FSH) and luteinizing hormone (LH), and lowered etradiol (E2) serum levels at a dose of 15 and 45 mg/kg in female rats. Ovarian lymphocytosis, vascular dilatation and congestion, inflammatory cell infiltration, and increase in apoptotic cells were found in ovary tissues in exposure groups. For male rats, the weights decreased gradually, the ratio of epididymis weight over body weight increased, the motility of rat sperm changed, and the levels of FSH and testosterone (T) diminished. Pathological results showed the shedding of epithelial cells of raw seminiferous tubule, disordered arrangement of cells in the tube, and the appearance of cell apoptosis and death in the exposure group. At the same time, Ni NPs resulted in a change of the reproductive index and the offspring development of rats. Further research is needed to elucidate exposure to human populations and mechanism of actions. PMID:25407529

  6. Differential effects of the histamine H3 receptor agonist methimepip on dentate granule cell excitability, paired-pulse plasticity and long-term potentiation in prenatal alcohol-exposed rats

    PubMed Central

    Varaschin, Rafael K.; Rosenberg, Martina J.; Hamilton, Derek A.; Savage, Daniel D.

    2016-01-01

    We previously reported that prenatal alcohol-induced deficits in dentate gyrus (DG) long-term potentiation (LTP) are ameliorated by the histamine H3 receptor inverse agonist ABT-239. ABT-239 did not enhance LTP in control rats, suggesting a heightened H3 receptor-mediated inhibition of glutamate release in prenatal alcohol-exposed (PAE) offspring. As the modulation of glutamate release is one important facet of LTP, we examined the effect of methimepip, a histamine H3 receptor agonist, on DG granule cell excitability, glutamate release and LTP in control and PAE rats. Long-Evans rat dams voluntarily consumed either a 0% or 5% ethanol solution four hours daily throughout gestation. Male adult offspring were anesthetized with urethane and electrodes implanted into the entorhinal cortex and DG. PAE reduced coupling of excitatory post-synaptic field potentials to population spikes, an effect mimicked in control rats treated with 1 mg/kg methimepip. Methimepip decreased release probability in controls but not in PAE offspring. GABAergic feedback inhibition of granule cell responsiveness was not affected by either PAE or methimepip. PAE reduced LTP in the DG, another effect mimicked in methimepip-treated control rats. Again, methimepip did not exacerbate the PAE-induced LTP deficit. Thus, while methimepip treatment of control rats mimicked some baseline and activity-dependent deficits observed in saline-treated PAE offspring, methimepip treatment of PAE rats did not exacerbate these deficits. Whether the absence of an added methimepip effect in PAE offspring is a consequence of a “floor effect” for the responses measured or is due to differential drug dose responsiveness will require further investigation. Further, more detailed studies of H3 receptor-mediated responses in vitro may provide clearer insights into the role of the H3 receptor regulation of excitatory transmission at the perforant path - DG synapse in PAE rats. PMID:24818819

  7. Genome-Wide DNA Methylation Profiling Reveals Epigenetic Changes in the Rat Nucleus Accumbens Associated With Cross-Generational Effects of Adolescent THC Exposure.

    PubMed

    Watson, Corey T; Szutorisz, Henrietta; Garg, Paras; Martin, Qammarah; Landry, Joseph A; Sharp, Andrew J; Hurd, Yasmin L

    2015-12-01

    Drug exposure during critical periods of development is known to have lasting effects, increasing one's risk for developing mental health disorders. Emerging evidence has also indicated the possibility for drug exposure to even impact subsequent generations. Our previous work demonstrated that adolescent exposure to Δ(9)-tetrahydrocannabinol (THC), the main psychoactive component of marijuana (Cannabis sativa), in a Long-Evans rat model affects reward-related behavior and gene regulation in the subsequent (F1) generation unexposed to the drug. Questions, however, remained regarding potential epigenetic consequences. In the current study, using the same rat model, we employed Enhanced Reduced Representation Bisulfite Sequencing to interrogate the epigenome of the nucleus accumbens, a key brain area involved in reward processing. This analysis compared 16 animals with parental THC exposure and 16 without to characterize relevant systems-level changes in DNA methylation. We identified 1027 differentially methylated regions (DMRs) associated with parental THC exposure in F1 adults, each represented by multiple CpGs. These DMRs fell predominantly within introns, exons, and intergenic intervals, while showing a significant depletion in gene promoters. From these, we identified a network of DMR-associated genes involved in glutamatergic synaptic regulation, which also exhibited altered mRNA expression in the nucleus accumbens. These data provide novel insight into drug-related cross-generational epigenetic effects, and serve as a useful resource for investigators to explore novel neurobiological systems underlying drug abuse vulnerability.

  8. Stimulation-Evoked Dopamine Release in the Nucleus Accumbens Following Cocaine Administration in Rats Perinatally Exposed to Polychlorinated Biphenyls

    PubMed Central

    Sable, Helen J. K.

    2013-01-01

    Exposure to polychlorinated biphenyls (PCBs) alters brain dopamine (DA) concentrations and DA receptor/transporter function, suggesting the reinforcing properties of drugs of abuse acting on the DA system may be affected by PCB exposure. Female Long-Evans rats were orally exposed to 0, 3, or 6mg/kg/day PCBs from 4 weeks prior to breeding until litters were weaned on postnatal day 21. In vivo fixed potential amperometry (FPA) was used in adult anesthetized offspring to determine whether perinatal PCB exposure altered (1) presynaptic DA autoreceptor (DAR) sensitivity, (2) electrically evoked nucleus accumbens (NAc) DA efflux following administration of cocaine, and (3) the rate of depletion of presynaptic DA stores. One adult male and female littermate were tested using FPA following a single injection of cocaine (20mg/kg ip), whereas a second adult male and female littermate were tested following the last of seven daily cocaine injections of the same dose. The carbon fiber recording microelectrode was positioned in the NAc core, and DA oxidation currents (i.e., DA release) evoked by brief stimulation of the medial forebrain bundle (MFB) were quantified before and after administration of cocaine. PCB-exposed rats exhibited enhanced stimulation-evoked DA release (relative to baseline) following a single injection of cocaine. Although nonexposed controls exhibited typical DA sensitization following repeated cocaine administration, this effect was attenuated in PCB-exposed rats. In addition, DAR sensitivity was higher (males only), and the rate of depletion of presynaptic DA stores was greater in PCB-exposed animals relative to nonexposed controls. These results indicate that perinatal PCB exposure can modify DA synaptic transmission in the NAc in a manner previously shown to alter the reinforcing properties of cocaine. PMID:23912914

  9. The effects of 17 alpha-methyltestosterone, methandrostenolone, and nandrolone decanoate on the rat estrous cycle.

    PubMed

    Blasberg, M E; Langan, C J; Clark, A S

    1997-02-01

    In a series of four separate experiments, the effects of anabolic-androgenic steroid (AAS) compounds on the estrous cycle of adult Long-Evans rats were examined. Sexual receptivity, vaginal cytology, and body weight were monitored throughout a 2-week baseline, AAS treatment, and recovery periods. In Experiments 1-3, subjects were administered 17 alpha-methyltestosterone, methandrostenolone, or nandrolone decanoate at doses selected to mimic the human abuse levels of each compound. In these studies, the highest doses of 17 alpha-methyltestosterone (7.5 mg/kg) and nandrolone decanoate (5.6 mg/kg) disrupted behavioral and vaginal cyclicity, whereas the highest dose of methandrostenolone (3.75 mg/kg) appeared to have slightly less robust effects. To compare effects on estrous cyclicity across AAS compounds, subjects in Experiment 4 received a single high dose (7.5 mg/kg) of each compound for 2 weeks. At this dose, all AAS compounds interfered with vaginal cyclicity, although effects on behavioral cyclicity and uterine weight were not uniform. Across all 4 experiments, AAS effects on body weight were minimal. The short-term administration of AAS compounds at levels commonly used by humans disrupts female neuroendocrine function in a dose-dependent manner. PMID:9035257

  10. Cocaine self-administration punished by intravenous histamine in adolescent and adult rats

    PubMed Central

    Holtz, Nathan A.; Carroll, Marilyn E.

    2016-01-01

    Adolescence is a transitional phase marked by a heightened vulnerability to substances of abuse. It has been hypothesized that both increased sensitivity to reward and decreased sensitivity to aversive events may drive drug-use liability during this phase. To investigate possible age-related differences in sensitivity to the aversive consequences of drug use, adolescent and adult rats were compared on self-administration of cocaine before, during, and after a 10-day period in which an aversive agent, histamine, was added to the cocaine solution. Adult and adolescent female rats were trained to self-administer intravenous cocaine (0.4 mg/kg/infusion) over 10 sessions (2 h/session; 2 sessions/day). Histamine (4 mg/kg/infusion) was then added directly into the cocaine solution for the next 10 sessions. Finally, the cocaine/histamine solution was replaced with a cocaine-only solution, and rats continued to self-administer cocaine (0.4 mg/kg) for 20 sessions. Compared with adolescent rats, adult rats showed a greater decrease in cocaine self-administration when it was punished with intravenous histamine compared with their baseline cocaine self-administration rates. These results suggest that differences in the sensitivity to negative consequences of drug use may partially explain developmental differences in drug use vulnerability. PMID:25769092

  11. Impact of prenatal and acute methamphetamine exposure on behaviour of adult male rats.

    PubMed

    Schutová, B; Hrubá, L; Pometlová, M; Slamberová, R

    2009-01-01

    Psychostimulants have been shown to alter behaviour in both rats and humans. The aim of the present study was: (1) to assess the effect of prenatal and acute methamphetamine (MA) administration on behaviour in adult male rats and (2) to find out if the prenatal exposure to MA increases sensitivity to acute MA application in adulthood. Behaviour of adult male rats prenatally exposed to MA (5 mg/kg) or no drug was tested in Open field (OF) and Elevated plus maze (EPM). Half of the animals were injected with MA (1 mg/kg) subcutaneously 30 minutes prior to testing. Locomotion, exploration, comforting behaviour and anxiety were evaluated in the OF, while anxiety and exploratory behaviour were assessed in the EPM. Our results showed that prenatal MA did not have an effect on baseline behaviour in either of the tests. By contrast, acute MA increased overall psychomotor activity by increasing locomotion and exploratory behaviour and decreasing comforting behaviour. Moreover, adult rats prenatally exposed to MA were more sensitive to the effects of acute MA on exploration. In addition, acute MA application decreased anxiety in the OF as well as in the EPM. Our present study, thus, demonstrates that acute MA increases overall psychomotor activity and decreases anxiety to novel environment. To further support our hypothesis that prenatal MA exposure increases sensitivity to drugs in adulthood, studies investigating the levels of dopamine in the rat brain after prenatal MA exposure are planned.

  12. Muscle mechanical properties of adult and older rats submitted to exercise after immobilization

    PubMed Central

    Kodama, Fábio Yoshikazu; Camargo, Regina Celi Trindade; Job, Aldo Eloizo; Ozaki, Guilherme Akio Tamura; Koike, Tatiana Emy; Camargo Filho, José Carlos Silva

    2012-01-01

    Objectives To describe the effects of immobilization, free remobilization and remobilization by physical exercise about mechanical properties of skeletal muscle of rats of two age groups. Methods 56 Wistar rats divided into two groups according to age, an adult group (five months) and an older group (15 months). These groups were subdivided in: control, immobilized, free remobilized and remobilized by physical exercise. The pelvic limb of rats was immobilized for seven days. The exercise protocol consisted of five swimming sessions, once per day and 25 minutes per session. The gastrocnemius muscle was subjected to tensile tests, and evaluated the properties: load at the maximum limit, stretching at the maximum limit and stiffness. Results The immobilization reduced the values of load at the maximum limit and the remobilization protocols were not sufficient to restore control levels in adult group and older rats. The stretching at the maximum limit differs only in the older group. Conclusions The immobilization reduces the muscle's ability to bear loads and exercise protocol tends to restore the default at control values in adult and older rats. The age factor only interfered in the stretching at the maximum limit, inducing a reduction of this property in the post-immobilization. Level of Evidence II, Investigating the Results of Treatment. PMID:24453606

  13. Cocaine self-administration punished by intravenous histamine in adolescent and adult rats.

    PubMed

    Holtz, Nathan A; Carroll, Marilyn E

    2015-06-01

    Adolescence is a transitional phase marked by a heightened vulnerability to substances of abuse. It has been hypothesized that both increased sensitivity to reward and decreased sensitivity to aversive events may drive drug-use liability during this phase. To investigate possible age-related differences in sensitivity to the aversive consequences of drug use, adolescent and adult rats were compared on self-administration of cocaine before, during, and after a 10-day period in which an aversive agent, histamine, was added to the cocaine solution. Adult and adolescent female rats were trained to self-administer intravenous cocaine (0.4 mg/kg/infusion) over 10 sessions (2 h/session; 2 sessions/day). Histamine (4 mg/kg/infusion) was then added directly into the cocaine solution for the next 10 sessions. Finally, the cocaine/histamine solution was replaced with a cocaine-only solution, and rats continued to self-administer cocaine (0.4 mg/kg) for 20 sessions. Compared with adolescent rats, adult rats showed a greater decrease in cocaine self-administration when it was punished with intravenous histamine compared with their baseline cocaine self-administration rates. These results suggest that differences in the sensitivity to negative consequences of drug use may partially explain developmental differences in drug use vulnerability.

  14. Restricted feeding facilitates time-place learning in adult rats.

    PubMed

    Lukoyanov, Nikolai V; Pereira, Pedro A; Mesquita, Rui M; Andrade, José P

    2002-08-21

    Many species can acquire time-of-day discrimination when tested in food reinforced place learning tasks. It is believed that this type of learning is dependent upon the ability of animals to consult their internal circadian pacemakers entrained by various environmental zeitgebers, such as light-dark cycles and scheduled restricted feeding. In the present study, we examined, (1) whether rats can acquire time-of-day discrimination in an aversively motivated water maze task wherein an escape platform is located in one position in the morning and in another position in the afternoon; (2) whether time-of-day cues provided by the light- and feeding-entrainable pacemakers may have divergent impacts upon the ability of rats to learn this task. Two groups of rats, both maintained on 12-h light:12-h dark cycle, were used; in one group, animals had free access to food, whereas in the other, they were subjected to a restricted feeding protocol (60% of food consumed by rats fed ad libitum, once daily). Despite the heightened difficulty of the task, food-restricted rats were apparently able to acquire associations between two different platform positions and two different times of day, as indicated by the fact that the percentage of discrimination errors in this group declined progressively, as a function of training, and stabilized at the level of 22+/-9%. In contrast, rats that were fed ad libitum, even after extensive training, failed to perform the task above level of chance. These data indicate that time-place learning is a universal, reward-nonspecific, cognitive phenomenon. They furthermore suggest that the ability of animals to integrate spatial and temporal information can be dependent on the access to timing stimuli provided by the feeding-entrainable circadian system.

  15. Trading new neurons for status: Adult hippocampal neurogenesis in eusocial Damaraland mole-rats.

    PubMed

    Oosthuizen, M K; Amrein, I

    2016-06-01

    Diversity in social structures, from solitary to eusocial, is a prominent feature of subterranean African mole-rat species. Damaraland mole-rats are eusocial, they live in colonies that are characterized by a reproductive division of labor and a subdivision into castes based on physiology and behavior. Damaraland mole-rats are exceptionally long lived and reproductive animals show delayed aging compared to non-reproductive animals. In the present study, we described the hippocampal architecture and the rate of hippocampal neurogenesis of wild-derived, adult Damaraland mole-rats in relation to sex, relative age and social status or caste. Overall, Damaraland mole-rats were found to have a small hippocampus and low rates of neurogenesis. We found no correlation between neurogenesis and sex or relative age. Social status or caste was the most prominent modulator of neurogenesis. An inverse relationship between neurogenesis and social status was apparent, with queens displaying the lowest neurogenesis while the worker mole-rats had the most. As there is no natural progression from one caste to another, social status within a colony was relatively stable and is reflected in the level of neurogenesis. Our results correspond to those found in the naked mole-rat, and may reflect an evolutionary and environmentally conserved trait within social mole-rat species. PMID:26979050

  16. Effects of neonatal treatment with the TRPV1 agonist, capsaicin, on adult rat brain and behaviour.

    PubMed

    Newson, Penny N; van den Buuse, Maarten; Martin, Sally; Lynch-Frame, Ann; Chahl, Loris A

    2014-10-01

    Treatment of neonatal rats with the transient receptor potential vanilloid 1 (TRPV1) channel agonist, capsaicin, produces life-long loss of sensory neurons expressing TRPV1 channels. Previously it was shown that rats treated on day 2 of life with capsaicin had behavioural hyperactivity in a novel environment at 5-7 weeks of age and brain changes reminiscent of those found in subjects with schizophrenia. The objective of the present study was to investigate brain and behavioural responses of adult rats treated as neonates with capsaicin. It was found that the brain changes found at 5-7 weeks in rats treated as neonates with capsaicin persisted into adulthood (12 weeks) but were less in older rats (16-18 weeks). Increased prepulse inhibition (PPI) of acoustic startle was found in these rats at 8 and 12 weeks of age rather than the deficit commonly found in animal models of schizophrenia. Subjects with schizophrenia also have reduced flare responses to niacin and methylnicotinate proposed to be mediated by prostaglandin D2 (PGD2). Flare responses are accompanied by cutaneous plasma extravasation. It was found that the cutaneous plasma extravasation responses to methylnicotinate and PGD2 were reduced in capsaicin-treated rats. In conclusion, several neuroanatomical changes observed in capsaicin-treated rats, as well as the reduced cutaneous plasma extravasation responses, indicate that the role of TRPV1 channels in schizophrenia is worthy of investigation.

  17. Prenatal Choline Availability Alters the Context Sensitivity of Pavlovian Conditioning in Adult Rats

    ERIC Educational Resources Information Center

    Lamoureux, Jeffrey A.; Meck, Warren H.; Williams, Christina L.

    2008-01-01

    The effects of prenatal choline availability on Pavlovian conditioning were assessed in adult male rats (3-4 mo). Neither supplementation nor deprivation of prenatal choline affected the acquisition and extinction of simple Pavlovian conditioned excitation, or the acquisition and retardation of conditioned inhibition. However, prenatal choline…

  18. Prenatal exposure to vapors of gasoline-ethanol blends causes few cognitive deficits in adult rats

    EPA Science Inventory

    Developmental exposure to inhaled ethanol-gasoline fuel blends is a potential public health concern. Here we assessed cognitive functions in adult offspring of pregnant rats that were exposed to vapors of gasoline blended with a range of ethanol concentrations, including gasoli...

  19. PREPUBERTAL EXPOSURES TO COMPOUNDS THAT INCREASE PROLACTIN SECRETION IN THE MALE RAT: EFFECTS ON ADULT PROSTATE

    EPA Science Inventory

    Prepubertal exposure to compounds that increase prolactin secretion in the male rat: effects on the adult prostate.

    Stoker TE, Robinette CL, Britt BH, Laws SC, Cooper RL.

    Endocrinology Branch, Reproductive Toxicology Division, National Health and Environmental Effec...

  20. Radial glia-like cells persist in the adult rat brain.

    PubMed

    Gubert, Fernanda; Zaverucha-do-Valle, Camila; Pimentel-Coelho, Pedro M; Mendez-Otero, Rosalia; Santiago, Marcelo F

    2009-03-01

    During development, radial glia cells contribute to neuronal migration and neurogenesis, and differentiate into astrocytes by the end of the developmental period. Recently, it was demonstrated that during development, radial glia cells, in addition to their role in migration, also give rise to neuroblasts. Furthermore, radial glial cells remain in the adult brain as adult neural stem cells (NSC) in the subventricular zone (SVZ) around the lateral ventricles (LVs), and generate new neurons continuously throughout adulthood. In this study, we used immunohistochemical and morphological methods to investigate the presence of radial glia-like cells around the LVs during the postnatal development period until adulthood in rats. In all ages of rats studied, we identified cells with morphological and immunocytochemical features that are similar to the radial glia cells found in the embryonic brain. Similarly to the radial glia, these cells express nestin and vimentin, and have a radial morphology, extending perpendicularly as processes from the ventricle wall. These cells also express GFAP, GLAST, and Pax6, and proliferate. In the brains of adult rats, we identified cells with relatively long processes (up to 600 mum) in close apposition with migrating neuroblasts. Our results showed that the radial glia-like cells present in the adult rat brain share several morphological and functional characteristics with the embryonic radial glia. We suggest that the embryonic radial glia cells located around the LV walls do not complete their transformation into astrocytes, but rather persist in adulthood.

  1. The role of apelin in the modulation of gastric and pancreatic enzymes activity in adult rats.

    PubMed

    Antuschevich, H; Kapica, M; Krawczynska, A; Herman, A; Kato, I; Kuwahara, A; Zabielski, R

    2016-06-01

    Apelin is considered as important gut regulatory peptide ligand of APJ receptor with a potential physiological role in gastrointestinal cytoprotection, regulation of food intake and drinking behavior. Circulating apelin inhibits secretion of pancreatic juice through vagal- cholecystokinin-dependent mechanism and reduces local blood flow. Our study was aimed to determine the effect of fundectomy and intraperitoneal or intragastric administration of apelin-13 on pancreatic and gastric enzymes activities in adult rats. Fundectomy is a surgical removal of stomach fundus - maine site apelin synthesis. Three independent experiments were carried out on Wistar rats. In the first and second experiment apelin-13 was given by intragastric or intraperitoneal way twice a day for 10 days (100 nmol/kg b.w.). Control groups received the physiological saline respectively. In the third experiment the group of rats after fundectomy were used. Fundectomized rats did not receive apelin and the rats from control group were 'sham operated'. At the end of experiment rats were sacrificed and blood from rats was withdrawn for apelin and CCK (cholecystokinin) radioimmunoassay analysis and pancreas and stomach tissues were collected for enzyme activity analyses. Intragastric and intraperitoneal administrations of apelin-13 increased basal plasma CCK level and stimulated gastric and pancreatic enzymes activity in rats. In animals after fundectomy decreased activity of studied enzymes was observed, as well as basal plasma apelin and CCK levels. In conclusion, apelin can effects on CCK release and stimulates some gastric and pancreatic enzymes activity in adult rats while fudectomy suppresses those processes. Changes in the level of pancreatic lipase activity point out that apelin may occurs as a regulator of lipase secretion.

  2. The role of apelin in the modulation of gastric and pancreatic enzymes activity in adult rats.

    PubMed

    Antuschevich, H; Kapica, M; Krawczynska, A; Herman, A; Kato, I; Kuwahara, A; Zabielski, R

    2016-06-01

    Apelin is considered as important gut regulatory peptide ligand of APJ receptor with a potential physiological role in gastrointestinal cytoprotection, regulation of food intake and drinking behavior. Circulating apelin inhibits secretion of pancreatic juice through vagal- cholecystokinin-dependent mechanism and reduces local blood flow. Our study was aimed to determine the effect of fundectomy and intraperitoneal or intragastric administration of apelin-13 on pancreatic and gastric enzymes activities in adult rats. Fundectomy is a surgical removal of stomach fundus - maine site apelin synthesis. Three independent experiments were carried out on Wistar rats. In the first and second experiment apelin-13 was given by intragastric or intraperitoneal way twice a day for 10 days (100 nmol/kg b.w.). Control groups received the physiological saline respectively. In the third experiment the group of rats after fundectomy were used. Fundectomized rats did not receive apelin and the rats from control group were 'sham operated'. At the end of experiment rats were sacrificed and blood from rats was withdrawn for apelin and CCK (cholecystokinin) radioimmunoassay analysis and pancreas and stomach tissues were collected for enzyme activity analyses. Intragastric and intraperitoneal administrations of apelin-13 increased basal plasma CCK level and stimulated gastric and pancreatic enzymes activity in rats. In animals after fundectomy decreased activity of studied enzymes was observed, as well as basal plasma apelin and CCK levels. In conclusion, apelin can effects on CCK release and stimulates some gastric and pancreatic enzymes activity in adult rats while fudectomy suppresses those processes. Changes in the level of pancreatic lipase activity point out that apelin may occurs as a regulator of lipase secretion. PMID:27512001

  3. Juvenile play conditions sexual partner preference in adult female rats.

    PubMed

    Paredes-Ramos, Pedro; Miquel, Marta; Manzo, Jorge; Coria-Avila, Genaro A

    2011-10-24

    Rats can display a conditioned partner preference for individuals that bear an odor previously associated with sexual reward. Herein we tested the possibility that odors associated with the reward induced by social play in prepubescent rats would induce a conditioned partner preference in adulthood. Two groups of 31-day-old, single-housed female rats were formed, and were given daily 30-min periods of social play with scented females. In one group, almond scent was paired with juvenile play during conditioning trials, whereas lemon scent functioned as a novel odor in the final test. The counterbalanced group received the opposite association. At age 42, females were tested for play partner preference with two males, one almond-scented and one lemon-scented. In both groups females displayed a play partner preference only for males scented with the paired odor. They were ovariectomized, hormone-primed, and at age 55 were tested for sexual partner preference with two scented stud males. Females displayed a sexual preference towards males scented with the paired odor as observed with more visits, solicitations, hops and darts, intromissions and ejaculations. These results indicate that olfactory stimuli paired with juvenile play affects later partner choice for play as well as for sex in female rats.

  4. Adversity before Conception Will Affect Adult Progeny in Rats

    ERIC Educational Resources Information Center

    Shachar-Dadon, Alice; Schulkin, Jay; Leshem, Micah

    2009-01-01

    The authors investigated whether adversity in a female, before she conceives, will influence the affective and social behavior of her progeny. Virgin female rats were either undisturbed (controls) or exposed to varied, unpredictable, stressors for 7 days (preconceptual stress [PCS]) and then either mated immediately after the end of the stress…

  5. Effect of Phaleria macrocarpa on Sperm Characteristics in Adult Rats

    PubMed Central

    Parhizkar, Saadat; Yusoff, Maryam Jamielah; Dollah, Mohammad Aziz

    2013-01-01

    Purpose: The purpose of this study was to determine the effects of Phaleria macrocarpa (PM) on male fertility by assessing its effect on the sperm characteristics which included the sperm count, motility, viability and morphology. Methods: Eighteen male rats were equally divided into three groups. Each group of rats was orally supplemented for 7 weeks either with PM aqueous extract (240 mg/kg), distilled water (0 mg/kg) or testosterone hormone, Andriol® Testocaps™ (4 mg/kg) respectively. On the last day of supplementation period, the rats were sacrificed and sperm was obtained from cauda epididymis via orchidectomy. The sperm count, motility, viability and morphology were determined. Results: PM aqueous extract significantly increased (p<0.05) the percentage of sperm viability. However, there was no significant effect of PM on the percentage of both sperm motility and morphology. The mean of body weight declined significantly in rats supplemented with PM aqueous extract compared to control groups (p<0.05). Conclusion: The results showed that PM significantly increased sperm viability without changing the sperm motility and morphology. Hence, this study suggests that PM offers an alternative way to improve male fertility by improving the sperm quality. PMID:24312859

  6. Prenatal lipopolysaccharide exposure increases depression-like behaviors and reduces hippocampal neurogenesis in adult rats.

    PubMed

    Lin, Yu-Lung; Wang, Sabrina

    2014-02-01

    Major depression is one of the most prevalent mental disorders in the population. In addition to genetic influences, disturbances in fetal nervous system development might be a contributing factor. Maternal infection during pregnancy may affect fetal brain development and consequently lead to neurological and mental disorders. Previously, we used low-dose lipopolysaccharide (LPS) exposure on embryonic day 10.5 to mimic mild maternal infection in rats and found that dopaminergic and serotonergic neurons were reduced in the offspring. The offspring also showed more anxiety-like behavior and an enhanced stress response. In the present study we used forced swim test and chronic mild stress challenge to assess depression-like behaviors in the affected offspring and examined their adult hippocampal neurogenesis and brain-derived neurotrophic factor (BDNF) concentration. Our results showed that prenatally LPS-exposed rats (LPS rats) displayed more depression-like behaviors and had reduced adult neurogenesis and BDNF. The behavioral abnormalities and reduction in adult neurogenesis could be reversed by chronic fluoxetine (FLX) treatment. This study demonstrates that during the critical time of embryonic development LPS exposure can produce long-term behavioral changes and reduction in adult neurogenesis. The findings of enhanced depression-like behaviors, reduced adult neurogenesis, and their responsiveness to chronic antidepressant treatment suggest that prenatal LPS exposure could serve as an animal model of depression.

  7. Dermal penetration of [14C]captan in young and adult rats.

    PubMed

    Fisher, H L; Hall, L L; Sumler, M R; Shah, P V

    1992-07-01

    Age dependence in dermal absorption has been a major concern in risk assessment. Captan, a chloroalkyl thio heterocyclic fungicide, was selected for study of age dependence as representative of this class of pesticides. Dermal penetration of [14C]captan applied at 0.286 mumol/cm2 was determined in young (33-d-old) and adult (82-d-old) female Fischer 344 rats in vivo and by two in vitro methods. Dermal penetration in vivo at 72 h was about 9% of the recovered dose in both young and adult rats. The percentage penetration was found to increase as dosage (0.1, 0.5, 2.7 mumol/cm2) decreased. Two in vitro methods gave variable dermal penetration values compared with in vivo results. A static system yielded twofold higher dermal penetration values compared with in vivo results for both young and adult rats. A flow system yielded higher dermal penetration values in young rats and lower penetration values in adults compared with in vivo results. Concentration in body, kidney, and liver was less in young than in adult rats given the same absorbed dosage. A physiological pharmacokinetic model was developed having a dual compartment for the treated skin and appeared to describe dermal absorption and disposition well. From this model, tissue/blood ratios of captan-derived radioactivity for organs were found to range from 0.35 to 3.4, indicating no large uptake or binding preferences by any organ. This preliminary pharmacokinetic model summarizes the experimental findings and could provide impetus for more complex and realistic models.

  8. Dentate gyrus-specific knockdown of adult neurogenesis impairs spatial and object recognition memory in adult rats

    PubMed Central

    Jessberger, Sebastian; Clark, Robert E.; Broadbent, Nicola J.; Clemenson, Gregory D.; Consiglio, Antonella; Lie, D. Chichung; Squire, Larry R.; Gage, Fred H.

    2009-01-01

    New granule cells are born throughout life in the dentate gyrus of the hippocampal formation. Given the fundamental role of the hippocampus in processes underlying certain forms of learning and memory, it has been speculated that newborn granule cells contribute to cognition. However, previous strategies aiming to causally link newborn neurons with hippocampal function used ablation strategies that were not exclusive to the hippocampus or that were associated with substantial side effects, such as inflammation. We here used a lentiviral approach to specifically block neurogenesis in the dentate gyrus of adult male rats by inhibiting WNT signaling, which is critically involved in the generation of newborn neurons, using a dominant-negative WNT (dnWNT). We found a level-dependent effect of adult neurogenesis on the long-term retention of spatial memory in the water maze task, as rats with substantially reduced levels of newborn neurons showed less preference for the target zone in probe trials >2 wk after acquisition compared with control rats. Furthermore, animals with strongly reduced levels of neurogenesis were impaired in a hippocampus-dependent object recognition task. Social transmission of food preference, a behavioral test that also depends on hippocampal function, was not affected by knockdown of neurogenesis. Here we identified a role for newborn neurons in distinct aspects of hippocampal function that will set the ground to further elucidate, using experimental and computational strategies, the mechanism by which newborn neurons contribute to behavior. PMID:19181621

  9. Effect of prenatal programming and postnatal rearing on glomerular filtration rate in adult rats.

    PubMed

    Lozano, German; Elmaghrabi, Ayah; Salley, Jordan; Siddique, Khurrum; Gattineni, Jyothsna; Baum, Michel

    2015-03-01

    The present study examined whether a prenatal low-protein diet programs a decrease in glomerular filtration rate (GFR) and an increase in systolic blood pressure (BP). In addition, we examined whether altering the postnatal nutritional environment of nursing neonatal rats affected GFR and BP when rats were studied as adults. Pregnant rats were fed a normal (20%) protein diet or a low-protein diet (6%) during the last half of pregnancy until birth, when rats were fed a 20% protein diet. Mature adult rats from the prenatal low-protein group had systolic hypertension and a GFR of 0.38 ± 0.03 versus 0.57 ± 0.05 ml·min(-1)·100 g body wt(-1) in the 20% group (P < 0.01). In cross-fostering experiments, mothers continued on the same prenatal diet until weaning. Prenatal 6% protein rats cross-fostered to a 20% mother on day 1 of life had a GFR of 0.53 ± 0.05 ml·min(-1)·100 g body wt(-1), which was not different than the 20% group cross-fostered to a different 20% mother (0.45 ± 0.04 ml·min(-1)·100 g body wt(-1)). BP in the 6% to 20% group was comparable with the 20% to 20% group. Offspring of rats fed either 20% or 6% protein diets during pregnancy and cross-fostered to a 6% mother had elevated BP but a comparable GFR normalized to body weight as the 20% to 20% control group. Thus, a prenatal low-protein diet causes hypertension and a reduction in GFR in mature adult offspring, which can be modified by postnatal rearing.

  10. Altered differentiation of CNS neural progenitor cells after transplantation into the injured adult rat spinal cord.

    PubMed

    Onifer, S M; Cannon, A B; Whittemore, S R

    1997-01-01

    Denervation of CNS neurons and peripheral organs is a consequence of traumatic SCI. Intraspinal transplantation of embryonic CNS neurons is a potential strategy for reinnervating these targets. Neural progenitor cell lines are being investigated as alternates to embryonic CNS neurons. RN33B is an immortalized neural progenitor cell line derived from embryonic rat raphe nuclei following infection with a retrovirus encoding the temperature-sensitive mutant of SV40 large T-antigen. Transplantation studies have shown that local epigenetic signals in intact or partially neuron-depleted adult rat hippocampal formation or striatum direct RN33B cell differentiation to complex multipolar morphologies resembling endogenous neurons. After transplantation into neuron-depleted regions of the hippocampal formation or striatum, RN33B cells were relatively undifferentiated or differentiated with bipolar morphologies. The present study examines RN33B cell differentiation after transplantation into normal spinal cord and under different lesion conditions. Adult rats underwent either unilateral lesion of lumbar spinal neurons by intraspinal injection of kainic acid or complete transection at the T10 spinal segment. Neonatal rats underwent either unilateral lesion of lumbar motoneurons by sciatic nerve crush or complete transection at the T10 segment. At 2 or 6-7 wk postinjury, lacZ-labeled RN33B cells were transplanted into the lumbar enlargement of injured and age-matched normal rats. At 2 wk posttransplantation, bipolar and some multipolar RN33B cells were found throughout normal rat gray matter. In contrast, only bipolar RN33B cells were seen in gray matter of kainic acid lesioned, sciatic nerve crush, or transection rats. These observations suggest that RN33B cell multipolar morphological differentiation in normal adult spinal cord is mediated by direct cell-cell interaction through surface molecules on endogenous neurons and may be suppressed by molecules released after SCI

  11. Juvenile stress affects anxiety-like behavior and limbic monoamines in adult rats.

    PubMed

    Luo, Xiao-Min; Yuan, San-Na; Guan, Xi-Ting; Xie, Xi; Shao, Feng; Wang, Wei-Wen

    2014-08-01

    Epidemiological evidence suggests that childhood and adolescent maltreatment is a major risk factor for mood disorders in adulthood. However, the mechanisms underlying the manifestation of mental disorders during adulthood are not well understood. Using a recently developed rat model for assessing chronic variable stress (CVS) during early adolescence (juvenility), we investigated the long-term effects of juvenile CVS on emotional and cognitive function and on monoaminergic activities in the limbic areas. During juvenility (postnatal days 27-33), rats in the stress group were exposed to variable stressors every other day for a week. Four weeks later, anhedonia was tested in the sucrose test, anxiety-like behaviors were assessed in the elevated plus-maze (EPM) and open field (OF) tests, and cortically mediated cognitive function was evaluated during an attentional set-shifting task (AST). After the behavioral tests, the rats were decapitated to determine limbic monoamine and metabolite levels. Adult rats stressed during juvenility exhibited higher anxiety-like behaviors, as evidenced by reduced locomotion and rearing behavior in the OF and fewer entries into the open arms in the EPM. There were no differences between the stressed rats and the controls in depressive-like anhedonia during the sucrose preference test or in cognitive function during the AST test in adulthood. In addition, the previously stressed rats exhibited increased dopamine (DA) and decreased 5-HIAA in the medial prefrontal cortex (mPFC) and decreased noradrenaline in the amygdala compared with controls. Furthermore, DA levels in the mPFC were correlated with adult anxious behaviors in the OF. These results suggest that juvenile stress induces long-term changes in the expression of anxiety-like behaviors and limbic monoaminergic activity in adult rats.

  12. Functional Myotube Formation from Adult Rat Satellite Cells in a Defined Serum-free System

    PubMed Central

    McAleer, Christopher W.; Rumsey, John W.; Stancescu, Maria; Hickman, James J.

    2016-01-01

    This manuscript describes the development of a culture system whereby mature contracting myotubes were formed from adult rat derived satellite cells. Satellite cells, extracted from the Tibialis Anterior (TA) of adult rats, were grown in defined serum-free growth and differentiation media, on a non-biological substrate, N-1[3-trimethoxysilyl propyl] diethylenetriamine. Myotubes were evaluated morphologically and immunocytochemically, using MyHC specific antibodies, as well as functionally using patch clamp electrophysiology to measure ion channel activity. Results indicated the establishment of the rapid expression of adult myosin isoforms that contrasts to their slow development in embryonic cultures. This culture system has applications in the understanding and treatment of age related muscle myopathy, muscular dystrophy, and for skeletal muscle engineering by providing a more relevant phenotype for both in vitro and in vivo applications. PMID:25683642

  13. Physiological and behavioral effects of acute ethanol hangover in juvenile, adolescent, and adult rats.

    PubMed

    Brasser, Susan M; Spear, Norman E

    2002-04-01

    This study examined differential responding of juvenile, adolescent, and adult rats after intoxication from an acute alcohol challenge. Experiment I generated blood ethanol curves for subjects 25, 35, or 110 days postnatal, after doses of 2.0 or 4.0 g/kg, assessing elimination rates and time of drug clearance. Experiment 2 compared ethanol's initial hypothermic and delayed hyperthermic effect across age by 48-hr temperature measurement with telemetry. At clearance or 24 hr after alcohol exposure, Experiment 3 tested subjects for changes in acoustic startle reactivity and ultrasonic vocalization (USV). Younger rats showed an absent or reduced tendency for residual hyperthermia, and adults showed alterations in USV observed as aftereffects of intoxication, despite greater initial blood alcohol levels and ethanol hypothermia in the former. The lesser ethanol hangover effects in weanlings and adolescents may be due in part to faster ethanol elimination at these ages compared with adults.

  14. The role of physical activity and feeding schedule on the kinetics of inhaled and oral toluene in rats.

    PubMed

    Bushnell, Philip J; Oshiro, Wendy M; Samsam, Tracey E; Klinger, Robert

    2007-11-01

    Published studies of the kinetics of toluene in rats have shown that its concentration in the blood rises during inhalation and falls after exposure stops; a similar uptake profile and longer persistence in blood typify the kinetics after oral exposure. Because rats in these studies are typically inactive during exposure, and behavioral tests of the acute effects of toluene require physical activity and altered feeding schedules, this study examined the role of physical activity and feeding status on the uptake of toluene given by the two routes. Two groups of adult male Long-Evans rats were conditioned to eat in the lab during the day. A group of "conditioned-active" (C-A) rats performed a lever-pressing task (LPT) for 1 h, either while inhaling toluene vapor (2000 ppm) or after a gavage dose (800 mg/kg toluene in corn oil). Another group of "conditioned-sedentary" (C-S) rats was dosed similarly but did not perform the LPT. A third group of "home cage" (HC) rats was not conditioned to eat during the day, but was maintained under typical laboratory conditions (eating at night in the home cage) before receiving toluene by gavage. In the conditioned rats, physical activity during inhalation exposure increased the concentrations of toluene in blood (from 35.8 +/- 2.5 to 45.2 +/- 3.2 mg/L after 60 min) and brain (from 73.4 +/- 5.3 to 103.0 +/- 3.8 mg/L after 60 min), but did not affect those concentrations after oral toluene. The time course of the uptake of toluene into blood and brain of HC rats followed that of published data. In contrast, toluene concentrations in the blood and brain of orally dosed conditioned rats fell rapidly compared to HC rats and published data (at 60 min after dosing, blood concentrations were: C-S rats, 17.2 +/- 1.7 mg/L; HC rats, 69.4 +/- 9.6 mg/L; and brain concentrations were: C-S rats, 30.9 +/- 5.0 mg/L; HC rats, 96.6 +/- 18.5 mg/L). These studies demonstrate the importance of physical activity for the uptake of inhaled toluene, and the

  15. Expression of transforming growth factor-beta in developing rat cerebral cortex: effects of prenatal exposure to ethanol.

    PubMed

    Miller, Michael W

    2003-06-01

    The effects of prenatal ethanol exposure on the spatiotemporal expression of transforming growth factor-beta (TGFbeta) and its receptors in developing rat cerebral cortex in vivo were examined. Pregnant Long-Evans rats were fed ad libitum with a diet containing ethanol from gestational day (G) 6 through G21 or were pair fed an isocaloric nonalcoholic liquid diet. A quantitative immunoblotting study showed that expression of TGFbeta ligands was differentially affected by ethanol; ethanol decreased TGFbeta1 expression fetally and in the mature cortex and increased TGFbeta2 at most ages. A complementary immunohistochemical experiment generated similar results so far as the timing of ligand expression was concerned. In both control and ethanol-treated rats, TGFbeta1 was expressed by cells in the two neocortical proliferative zones and neurons in the cortical plate. TGFbeta2 was expressed principally by radial glia and astrocytes in developing rats. In the adult, both ligands were expressed by glia and neurons. Ethanol virtually eliminated the TGFbeta1 expression in the perinatal subventricular zone. The TGFbeta2-positive radial glial labeling was transient and was lost earlier in ethanol-treated neonates than in controls. Concomitantly, the appearance of TGFbeta2-positive glia occurred earlier in the ethanol-treated rats. The expression of only one receptor (TGFbetaIr) was affected by ethanol; it was increased during the pre- and early postnatal periods. TGFbetaIr was expressed by glia perinatally and by all cell types in weanlings. As with TGFbeta2, ethanol exposure promoted the loss of TGFbetaIr expression in radial glia and the precocious expression among astrocytes. TGFbetaIIr was expressed primarily by neurons. Thus, TGFbeta ligands and receptors are strategically placed both in time and space to regulate cell proliferation and migration. Ethanol, which affects both of these processes, has marked effects on the TGFbeta system and apparently promotes the early

  16. Effect of seven days of spaceflight on hindlimb muscle protein, RNA and DNA in adult rats

    NASA Technical Reports Server (NTRS)

    Steffen, J. M.; Musacchia, X. J.

    1985-01-01

    Effects of seven days of spaceflight on skeletal muscle (soleus, gastrocnemius, EDL) content of protein, RNA and DNA were determined in adult rats. Whereas total protein contents were reduced in parallel with muscle weights, myofibrillar protein appeared to be more affected. There were no significant changes in absolute DNA contents, but a significant (P less than 0.05) increase in DNA concentration (microgram/milligram) in soleus muscles from flight rats. Absolute RNA contents were significantly (P less than 0.025) decreased in the soleus and gastrocnemius muscles of flight rats, with RNA concentrations reduced 15-30 percent. These results agree with previous ground-based observations on the suspended rat with unloaded hindlimbs and support continued use of this model.

  17. Impairment of male reproduction in adult rats exposed to hydroxyprogesterone caproate in utero

    NASA Astrophysics Data System (ADS)

    Pushpalatha, T.; Ramachandra Reddy, P.; Sreenivasula Reddy, P.

    Hydroxyprogesterone caproate is one of the most effective and widely used drugs for the treatment of uterine bleeding and threatened miscarriage in women. Hydroxyprogesterone caproate was administered to pregnant rats in order to assess the effect of intraperitoneal exposure to supranormal levels of hydroxyprogesterone caproate on the male reproductive potential in the first generation. The cauda epididymal sperm count and motility decreased significantly in rats exposed to hydroxyprogesterone caproate during embryonic development, when compared with control rats. The levels of serum testosterone decreased with an increase in follicle stimulating hormone and luteinizing hormone in adult rats exposed to hydroxyprogesterone caproate during the embryonic stage. It was suggested that the impairment of male reproductive performance could be mediated through the inhibition of testosterone production.

  18. Receiving of emotional signal of pain from conspecifics in laboratory rats.

    PubMed

    Nakashima, Satoshi F; Ukezono, Masatoshi; Nishida, Hiroshi; Sudo, Ryunosuke; Takano, Yuji

    2015-04-01

    Though recent studies have shown that rodents express emotions with their face, whether emotional expression in rodents has a communicative function between conspecifics is still unclear. Here, we demonstrate the ability of visual recognition of emotional expressions in laboratory rats. We found that Long-Evans rats avoid images of pain expressions of conspecifics but not those of neutral expressions. The results indicate that rats use visual emotional signals from conspecifics to adjust their behaviour in an environment to avoid a potentially dangerous place. Therefore, emotional expression in rodents, rather than just a mere 'expression' of emotional states, might have a communicative function. PMID:26064632

  19. Perinatal taurine exposure alters renal potassium excretion mechanisms in adult conscious rats.

    PubMed

    Roysommuti, Sanya; Malila, Pisamai; Lerdweeraphon, Wichaporn; Jirakulsomchok, Dusit; Wyss, J Michael

    2010-08-24

    Perinatal taurine exposure has long-term effects on the arterial pressure and renal function. This study tests its influence on renal potassium excretion in young adult, conscious rats. Female Sprague-Dawley rats were fed normal rat chow and given water alone (C), 3% beta-alanine in water (taurine depletion, TD) or 3% taurine in water (taurine supplementation, TS), either from conception until delivery (fetal period; TDF or TSF) or from delivery until weaning (lactation period; TDL or TSL). In Experiment 1, male offspring were fed normal rat chow and tap water, while in Experiment 2, beta-alanine and taurine were treated from conception until weaning and then female pups were fed normal rat chow and 5% glucose in drinking water (CG, TDG or TSG) or water alone (CW, TDW or TSW). At 7-8 weeks of age, renal potassium excretion was measured at rest and after an acute saline load (5% of body weight) in conscious, restrained rats. Although all male groups displayed similar renal potassium excretion, TSF rats slightly increased fractional potassium excretion at rest but not in response to saline load, whereas TDF did the opposite. Plasma potassium concentration was only slightly altered by the diet manipulations. In female offspring, none of the perinatal treatments significantly altered renal potassium excretion at rest or after saline load. High sugar intake slightly decreased potassium excretion at rest in TDG and TSG, but only the TDG group displayed a decreased response to saline load. The present data indicates that perinatal taurine exposure only mildly influences renal potassium excretion in adult male and female rats.

  20. The role of testicular hormones and luteinizing hormone in spatial memory in adult male rats.

    PubMed

    McConnell, Sarah E A; Alla, Juliet; Wheat, Elizabeth; Romeo, Russell D; McEwen, Bruce; Thornton, Janice E

    2012-04-01

    Attempts to determine the influence of testicular hormones on learning and memory in males have yielded contradictory results. The present studies examined whether testicular hormones are important for maximal levels of spatial memory in young adult male rats. To minimize any effect of stress, we used the Object Location Task which is a spatial working memory task that does not involve food or water deprivation or aversive stimuli for motivation. In Experiment 1 sham gonadectomized male rats demonstrated robust spatial memory, but gonadectomized males showed diminished spatial memory. In Experiment 2 subcutaneous testosterone (T) capsules restored spatial memory performance in gonadectomized male rats, while rats with blank capsules demonstrated compromised spatial memory. In Experiment 3, gonadectomized male rats implanted with blank capsules again showed compromised spatial memory, while those with T, dihydrotestosterone (DHT), or estradiol (E) capsules demonstrated robust spatial memory, indicating that T's effects may be mediated by its conversion to E or to DHT. Gonadectomized male rats injected with Antide, a gonadotropin-releasing hormone receptor antagonist which lowers luteinizing hormone levels, also demonstrated spatial memory, comparable to that shown by T-, E-, or DHT-treated males. These data indicate that testicular androgens are important for maximal levels of spatial working memory in male rats, that testosterone may be converted to E and/or DHT to exert its effects, and that some of the effects of these steroid hormones may occur via negative feedback effects on LH.

  1. Hepatoprotective activity of bacoside A against N-nitrosodiethylamine-induced liver toxicity in adult rats.

    PubMed

    Janani, Panneerselvam; Sivakumari, Kanakarajan; Parthasarathy, Chandrakesan

    2009-10-01

    N-Nitrosodiethylamine (DEN) is a notorious carcinogen, present in many environmental factors. DEN induces oxidative stress and cellular injury due to enhanced generation of reactive oxygen species; free radical scavengers protect the membranes from DEN-induced damage. The present study was designed to evaluate the protective effect of bacoside A (the active principle isolated from Bacopa monniera Linn.) on carcinogen-induced damage in rat liver. Adult male albino rats were pretreated with 15 mg/kg body weight/day of bacoside A orally (for 14 days) and then intoxicated with single necrogenic dose of N-nitrosodiethylamine (200 mg/kg bodyweight, intraperitonially) and maintained for 7 days. The liver weight, lipid peroxidation (LPO), and activity of serum marker enzymes (aspartate transaminases, alanine transaminases, lactate dehydrogenase, alkaline phosphatase, and gamma-glutamyl transpeptidase) were markedly increased in carcinogen-administered rats, whereas the activities of marker enzymes were near normal in bacoside A-pretreated rats. Activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutatione-S-transferase, and reduced glutathione) in liver also decreased in carcinogen-administered rats, which were significantly elevated in bacoside A-pretreated rats. It is concluded that pretreatment of bacoside A prevents the elevation of LPO and activity of serum marker enzymes and maintains the antioxidant system and thus protects the rats from DEN-induced hepatotoxicity.

  2. Histological effects of chronic administration of Phyllanthus amarus on the kidney of adult Wistar rat

    PubMed Central

    Adjene, Josiah Obaghwarhieywo; Nwose, Ezekiel Uba

    2010-01-01

    Background: Phyllanthus amarus is commonly used for treatment such as in gastro, urogenital diseases and infection. However, it is speculated to have some toxic effects such as renal tubular damage. Aims: This study was to investigate the histological effects of chronic administration of the herb on kidney of adult Wistar rats. Material and Methods: Rats of both sexes (n = 24), with average weight of 200g were randomly assigned into two treatments (A and B) and control (C) groups of 8 rats each. Rats in treatment groups (A) and (B) respectively received daily administration of 400mg and 800mg of aqueous Phyllanthus amarus, per 70kg body weight for 30days through the orogastric tube. The control group received distilled water through the same route. All rats were fed with grower's mash and given water liberally. The rats were sacrificed by cervical dislocation on the thirty-first day of the experiment and the kidneys were carefully dissected out and quickly fixed in 10% formal saline for histological study. Results: The observations indicate that rats in the treated groups showed some varying degree of distortion and disruption in microanatomy of the kidney including interstitial oedema and tubular necrosis, when compared to the control section. Conclusion: This report provides further evidence that medicinal use of Phyllanthus amarus has a potential adverse effect. This warrants further studies to establish or rule out any untoward side-effect of chronic renal dysfunctions. PMID:22624139

  3. Early exposure to bisphenol A alters neuron and glia number in the rat prefrontal cortex of adult males, but not females

    PubMed Central

    Sadowski, Renee N.; Wise, Leslie M.; Park, Pul Y.; Schantz, Susan L.; Juraska, Janice M.

    2014-01-01

    Previous work has shown that exposure to bisphenol A (BPA) during early development can alter sexual differentiation of the brain in rodents, although few studies have examined effects on areas of the brain associated with cognition. The current study examined if developmental BPA exposure alters the total number of neurons and glia in the medial prefrontal cortex (mPFC) in adulthood. Pregnant Long-Evans rats were orally exposed to 0, 4, 40, or 400 μg/kg BPA in corn oil throughout pregnancy. From postnatal days 1-9, pups were given daily oral doses of oil or BPA, at doses corresponding to those given during gestation. Brains were examined in adulthood, and the volume of layers 2/3 and layers 5/6 of the mPFC were parcellated. The density of neurons and glia in these layers was quantified stereologically with the optical disector, and density was multiplied by volume for each animal. Males exposed to 400 μg/kg BPA were found to have increased numbers of neurons and glia in layers 5/6. Although there were no significant effects of BPA in layers 2/3, the pattern of increased neuron number in males exposed to 400 μg/kg BPA was similar to that seen in layers 5/6. No effects of BPA were seen in females or in males exposed to the other doses of BPA. This study indicates that males are more susceptible to the long-lasting effects of BPA on anatomy of the mPFC, an area implicated in neurological disorders. PMID:25193849

  4. Effects of neonatal methamphetamine treatment on adult stress-induced corticosterone release in rats.

    PubMed

    Grace, Curtis E; Schaefer, Tori L; Herring, Nicole R; Williams, Michael T; Vorhees, Charles V

    2012-01-01

    In rats, neonatal (+)-methamphetamine (MA) exposure and maternal separation stress increase corticosterone during treatment and result in learning and memory impairments later in life. Early-life stress also changes later responses to acute stress. We tested the hypothesis that neonatal MA exposure would alter adult corticosterone after acute stress or MA challenge. Rats were treated with MA (10 mg/kg × 4/day), saline, or handling on postnatal (P) days 11-15 or 11-20 (days that lead to learning and memory impairments at this dose). As adults, corticosterone was measured before and after 15 min forced swim (FS) or 15 min forced confinement (FC), counterbalanced, and after an acute MA challenge (10 mg/kg) given last. FS increased corticosterone more than FC; order and stress type interacted but did not interact with treatment; treatment interacted with FS but not with FC. In the P11-15 regimen, MA-treated rats showed more rapid increases in corticosterone after FS than controls. In the P11-20 regimen, MA-treated rats showed a trend toward more rapid decrease in corticosterone after FS. No differences were found after MA challenge. The data do not support the hypothesis that neonatal MA causes changes in adult stress responsiveness to FS, FC, or an acute MA challenge.

  5. Defective copper binding to apo-ceruloplasmin in a rat model and patients with Wilson's disease.

    PubMed

    Kojimahara, N; Nakabayashi, H; Shikata, T; Esumi, M

    1995-06-01

    To examine the mechanism of decrease in serum ceruloplasmin (Cp) in Long-Evans Cinnamon (LEC) rats, a proposed model of Wilson's disease, we analyzed Cp products at the stages of transcription and translation. Northern blot analysis and immunoblot analysis showed that the level and the molecular size of Cp mRNA and protein in LEC rats were similar to those in control Long-Evans-Agouti (LEA) rats. However, the ferroxidase activity of Cp was significantly decreased in LEC rats. We separated serum Cp into two forms by native polyacrylamide gel electrophoresis with pH modification: one was a holo-Cp with copper and ferroxidase activity, and the other was an inactive apo-Cp without copper. Holo-Cp was the predominant form in LEA rats and normal humans, whereas apo-Cp was the major form in LEC rats and patients with Wilson's disease. The cosegregation of apo-Cp predominance with the disease in LEC rats was analyzed using backcross rats. Apo-Cp was dominant in 8 of 11 offspring with disease but in none of 19 normal offspring. These results indicate that a genetic disturbance of copper binding to apo-Cp may be closely associated with the pathogenesis in LEC rats, and probably in Wilson's disease.

  6. Beer promotes high levels of alcohol intake in adolescent and adult alcohol-preferring rats.

    PubMed

    Hargreaves, Garth A; Wang, Emyo Y J; Lawrence, Andrew J; McGregor, Iain S

    2011-08-01

    Previous studies suggest that high levels of alcohol consumption can be obtained in laboratory rats by using beer as a test solution. The present study extended these observations to examine the intake of beer and equivalent dilute ethanol solutions with an inbred line of alcohol-preferring P rats. In Experiment 1, male adolescent P rats and age-matched Wistar rats had access to either beer or equivalent ethanol solutions for 1h daily in a custom-built lickometer apparatus. In subsequent experiments, adolescent (Experiment 2) and adult (Experiment 3) male P rats were given continuous 24-h home cage access to beer or dilute ethanol solutions, with concomitant access to lab chow and water. In each experiment, the alcohol content of the beer and dilute ethanol solutions was gradually increased from 0.4, 1.4, 2.4, 3.4, 4.4, 5 to 10% EtOH (vol/vol). All three experiments showed a major augmentation of alcohol intake when rats were given beer compared with equivalent ethanol solutions. In Experiment 1, the overall intake of beer was higher in P rats compared with Wistar rats, but no strain difference was found during the 1-h sessions with plain ethanol consumption. Experiment 1 also showed that an alcohol deprivation effect was more readily obtained in rats with a history of consuming beer rather than plain ethanol solutions. In Experiments 2 and 3, voluntary beer intake in P rats represented ethanol intake of 10-15 g/kg/day, among the highest reported in any study with rats. This excessive consumption was most apparent in adolescent rats. Beer consumption markedly exceeded plain ethanol intake in these experiments except at the highest alcohol concentration (10%) tested. The advantage of using beer rather than dilute ethanol solutions in both selected and nonselected rat strains is therefore confirmed. Our findings encourage the use of beer with alcohol-preferring rats in future research that seeks to obtain high levels of alcohol self-administration.

  7. Cross-sensitization between testosterone and cocaine in adolescent and adult rats.

    PubMed

    Engi, Sheila A; Cruz, Fabio C; Crestani, Carlos C; Planeta, Cleopatra S

    2015-11-01

    Cocaine and anabolic-androgenic steroids are substances commonly co-abused. The use of anabolic steroids and cocaine has increased among adolescents. However, few studies investigated the consequences of the interaction between anabolic-androgenic steroids in animals' model of adolescence. We examined the effects of acute and repeated testosterone administration on cocaine-induced locomotor activity in adult and adolescent rats. Rats received ten once-daily subcutaneous (s.c.) injections of testosterone (10mg/kg) or vehicle. Three days after the last testosterone or vehicle injections rats received an intraperitoneal (i.p.) challenge injection of either saline or cocaine (10mg/kg). A different subset of rats was treated with a single injection of testosterone (10mg/kg) or vehicle and three days later was challenged with cocaine (10mg/kg, i.p.) or saline. Immediately after cocaine or saline injections the locomotor activity was recorded during forty minutes. Our results demonstrated that repeated testosterone induced locomotor sensitization to cocaine in adolescent but not adult rats.

  8. Behavioral changes in preweaning and adult rats exposed prenatally to low ionizing radiation

    SciTech Connect

    Norton, S.

    1986-04-01

    Seven behavioral tests were used to evaluate the postnatal behavior of rats after exposure on gestational Day 15 to 0, 25, 50, 75, or 125 r, whole body irradiation of the pregnant rat. Three tests were administered in the first 2 postnatal weeks (righting reflex, negative geotaxis, and reflex suspension); three tests were administered on postnatal Day 21 (modified open field, spatial maze, and continuous corridor). As adults, the rats were retested with the same tests as at 21 days and also in the running wheel. Dose-response decreases in body weight were greater in the younger rats. Some behavioral tests were not altered by irradiation, while others showed clear dose-response relationships, starting as low as 25 r. The early changes were characterized by light body weight, delays in behavioral development and hypoactivity, followed by recovery of some parameters with maturation. Eventually hyperactivity developed in adult rats after gestational irradiation. However, it cannot be concluded that either morphological or behavioral tests are more sensitive than neonatal body weight change for detection of damage from gestational irradiation.

  9. Aging-Dependent Changes in the Radiation Response of the Adult Rat Brain

    SciTech Connect

    Schindler, Matthew K. Forbes, M. Elizabeth; Robbins, Mike E.; Riddle, David R.

    2008-03-01

    Purpose: To assess the impact of aging on the radiation response in the adult rat brain. Methods and Materials: Male rats 8, 18, or 28 months of age received a single 10-Gy dose of whole-brain irradiation (WBI). The hippocampal dentate gyrus was analyzed 1 and 10 weeks later for sensitive neurobiologic markers associated with radiation-induced damage: changes in density of proliferating cells, immature neurons, total microglia, and activated microglia. Results: A significant decrease in basal levels of proliferating cells and immature neurons and increased microglial activation occurred with normal aging. The WBI induced a transient increase in proliferation that was greater in older animals. This proliferation response did not increase the number of immature neurons, which decreased after WBI in young rats, but not in old rats. Total microglial numbers decreased after WBI at all ages, but microglial activation increased markedly, particularly in older animals. Conclusions: Age is an important factor to consider when investigating the radiation response of the brain. In contrast to young adults, older rats show no sustained decrease in number of immature neurons after WBI, but have a greater inflammatory response. The latter may have an enhanced role in the development of radiation-induced cognitive dysfunction in older individuals.

  10. Cross-sensitization between testosterone and cocaine in adolescent and adult rats.

    PubMed

    Engi, Sheila A; Cruz, Fabio C; Crestani, Carlos C; Planeta, Cleopatra S

    2015-11-01

    Cocaine and anabolic-androgenic steroids are substances commonly co-abused. The use of anabolic steroids and cocaine has increased among adolescents. However, few studies investigated the consequences of the interaction between anabolic-androgenic steroids in animals' model of adolescence. We examined the effects of acute and repeated testosterone administration on cocaine-induced locomotor activity in adult and adolescent rats. Rats received ten once-daily subcutaneous (s.c.) injections of testosterone (10mg/kg) or vehicle. Three days after the last testosterone or vehicle injections rats received an intraperitoneal (i.p.) challenge injection of either saline or cocaine (10mg/kg). A different subset of rats was treated with a single injection of testosterone (10mg/kg) or vehicle and three days later was challenged with cocaine (10mg/kg, i.p.) or saline. Immediately after cocaine or saline injections the locomotor activity was recorded during forty minutes. Our results demonstrated that repeated testosterone induced locomotor sensitization to cocaine in adolescent but not adult rats. PMID:26150134

  11. Does prenatal methamphetamine exposure affect the drug-seeking behavior of adult male rats?

    PubMed

    Slamberová, Romana; Schutová, Barbora; Hrubá, Lenka; Pometlová, Marie

    2011-10-10

    Methamphetamine (MA) is one of the most frequently used illicit drugs worldwide and also one of the most common drugs abused by pregnant women. Repeated administration of psychostimulants induces behavioral sensitization in response to treatment of the same or related drugs in rodents. The effect of prenatal MA exposure on sensitivity to drugs in adulthood is not yet fully determined. Because our most recent studies demonstrated that prenatal MA (5mg/kg) exposure makes adult rats more sensitive to acute injection of the same drug, we were interested whether the increased sensitivity corresponds with the increased drug-seeking behavior. The aim of the present study was to examine the effect of prenatal MA exposure on drug-seeking behavior of adult male rats tested in the conditioned place preference (CPP). The following psychostimulant drugs were used as a challenge in adulthood: MA (5mg/kg), amphetamine (5mg/kg) and cocaine (10mg/kg). All psychostimulant drugs induced increased drug-seeking behavior in adult male rats. However, while MA and amphetamine-induced increase in drug-seeking behavior did not differ based on the prenatal drug exposure, prenatally MA-exposed rats displayed tolerance effect to cocaine in adulthood. In addition, prenatally MA-exposed rats had decreased weight gain after administration of MA or amphetamine, while the weight of prenatally MA-exposed rats stayed unchanged after cocaine administration. Defecation was increased by all the drugs (MA, amphetamine and cocaine), while only amphetamine increased the tail temperature. In conclusion, our results did not confirm our hypothesis that prenatal MA exposure increases drug-seeking behavior in adulthood in the CPP test.

  12. Effect of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) on Hormones of Energy Balance in a TCDD-Sensitive and a TCDD-Resistant Rat Strain

    PubMed Central

    Lindén, Jere; Lensu, Sanna; Pohjanvirta, Raimo

    2014-01-01

    One of the hallmarks of the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a drastically reduced feed intake by an unknown mechanism. To further elucidate this wasting syndrome, we followed the effects of a single large dose (100 μg/kg) of TCDD on the serum levels of several energy balance-influencing hormones, clinical chemistry variables, and hepatic aryl hydrocarbon receptor (AHR) expression in two rat strains that differ widely in their TCDD sensitivities, for up to 10 days. TCDD affected most of the analytes in sensitive Long-Evans rats, while there were few alterations in the resistant Han/Wistar strain. However, analyses of feed-restricted unexposed Long-Evans rats indicated several of the perturbations to be secondary to energy deficiency. Notable increases in ghrelin and glucagon occurred in TCDD-treated Long-Evans rats alone, which links these hormones to the wasting syndrome. The newly found energy balance regulators, insulin-like growth factor 1 and fibroblast growth factor 21 (FGF-21), appeared to function in concert in body weight loss-induced metabolic state, and FGF-21 was putatively linked to increased lipolysis induced by TCDD. Finally, we demonstrate a reverse set of changes in the AHR protein and mRNA response to TCDD and feed restriction, suggesting that AHR might function also as a physiological regulator, possibly involved in the maintenance of energy balance. PMID:25119860

  13. Prolonged performance of a high repetition low force task induces bone adaptation in young adult rats, but loss in mature rats.

    PubMed

    Massicotte, Vicky S; Frara, Nagat; Harris, Michele Y; Amin, Mamta; Wade, Christine K; Popoff, Steven N; Barbe, Mary F

    2015-12-01

    We have shown that prolonged repetitive reaching and grasping tasks lead to exposure-dependent changes in bone microarchitecture and inflammatory cytokines in young adult rats. Since aging mammals show increased tissue inflammatory cytokines, we sought here to determine if aging, combined with prolonged performance of a repetitive upper extremity task, enhances bone loss. We examined the radius, forearm flexor muscles, and serum from 16 mature (14-18 months of age) and 14 young adult (2.5-6.5 months of age) female rats after performance of a high repetition low force (HRLF) reaching and grasping task for 12 weeks. Young adult HRLF rats showed enhanced radial bone growth (e.g., increased trabecular bone volume, osteoblast numbers, bone formation rate, and mid-diaphyseal periosteal perimeter), compared to age-matched controls. Mature HRLF rats showed several indices of radial bone loss (e.g., decreased trabecular bone volume, and increased cortical bone thinning, porosity, resorptive spaces and woven bone formation), increased osteoclast numbers and inflammatory cytokines, compared to age-matched controls and young adult HRLF rats. Mature rats weighed more yet had lower maximum reflexive grip strength, than young adult rats, although each age group was able to pull at the required reach rate (4 reaches/min) and required submaximal pulling force (30 force-grams) for a food reward. Serum estrogen levels and flexor digitorum muscle size were similar in each age group. Thus, mature rats had increased bone degradative changes than in young adult rats performing the same repetitive task for 12 weeks, with increased inflammatory cytokine responses and osteoclast activity as possible causes. PMID:26517953

  14. Prolonged performance of a high repetition low force task induces bone adaptation in young adult rats, but loss in mature rats.

    PubMed

    Massicotte, Vicky S; Frara, Nagat; Harris, Michele Y; Amin, Mamta; Wade, Christine K; Popoff, Steven N; Barbe, Mary F

    2015-12-01

    We have shown that prolonged repetitive reaching and grasping tasks lead to exposure-dependent changes in bone microarchitecture and inflammatory cytokines in young adult rats. Since aging mammals show increased tissue inflammatory cytokines, we sought here to determine if aging, combined with prolonged performance of a repetitive upper extremity task, enhances bone loss. We examined the radius, forearm flexor muscles, and serum from 16 mature (14-18 months of age) and 14 young adult (2.5-6.5 months of age) female rats after performance of a high repetition low force (HRLF) reaching and grasping task for 12 weeks. Young adult HRLF rats showed enhanced radial bone growth (e.g., increased trabecular bone volume, osteoblast numbers, bone formation rate, and mid-diaphyseal periosteal perimeter), compared to age-matched controls. Mature HRLF rats showed several indices of radial bone loss (e.g., decreased trabecular bone volume, and increased cortical bone thinning, porosity, resorptive spaces and woven bone formation), increased osteoclast numbers and inflammatory cytokines, compared to age-matched controls and young adult HRLF rats. Mature rats weighed more yet had lower maximum reflexive grip strength, than young adult rats, although each age group was able to pull at the required reach rate (4 reaches/min) and required submaximal pulling force (30 force-grams) for a food reward. Serum estrogen levels and flexor digitorum muscle size were similar in each age group. Thus, mature rats had increased bone degradative changes than in young adult rats performing the same repetitive task for 12 weeks, with increased inflammatory cytokine responses and osteoclast activity as possible causes.

  15. Plasticity in the prefrontal cortex of adult rats

    PubMed Central

    Kolb, Bryan; Gibb, Robbin

    2015-01-01

    We review the plastic changes of the prefrontal cortex of the rat in response to a wide range of experiences including sensory and motor experience, gonadal hormones, psychoactive drugs, learning tasks, stress, social experience, metaplastic experiences, and brain injury. Our focus is on synaptic changes (dendritic morphology and spine density) in pyramidal neurons and the relationship to behavioral changes. The most general conclusion we can reach is that the prefrontal cortex is extremely plastic and that the medial and orbital prefrontal regions frequently respond very differently to the same experience in the same brain and the rules that govern prefrontal plasticity appear to differ for those of other cortical regions. PMID:25691857

  16. The effects of quinapril and atorvastatin on artery structure and function in adult spontaneously hypertensive rats.

    PubMed

    Yang, Lufang; Gao, Yu-Jing; Lee, Robert M K W

    2005-08-22

    We studied the combined treatment effects of quinapril and atorvastatin on blood pressure and structure and function of resistance arteries from adult spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY rats). Apoptotic cells were identified by in situ end labeling using the terminal deoxynucleotide transferase-mediated dUTP nick end labeling method. Vascular structure was measured using a morphometric protocol and confocal microscopy and a pressurized artery system was used to study vascular functions. We found that a combined treatment with quinapril and atorvastatin lowered systolic blood pressure in both adult SHR and WKY rats and decreased medial thickness and volume and the number of smooth muscle cell layers in mesenteric arteries, as well as media-to-lumen ratio in the interlobular arteries from SHR but not in those from WKY rats. The number of apoptotic smooth muscle cells was higher in the mesenteric arteries from control WKY rats than control SHR and treatment increased the number of apoptotic smooth muscle cells in the arteries from both SHR and WKY rats. Treatment with quinapril and atorvastatin reduced ventricular weight in SHR and normalized the augmented contractile responses to norepinephrine but did not alter the contraction to electric field stimulation. Relaxation responses to acetylcholine and sodium nitroprusside were not affected by the treatment. We conclude that a combined treatment with quinapril and atorvastatin lowered blood pressure and improved cardiac and vessel hypertrophy and vessel function. An increase in apoptotic smooth muscle cells may be one of the mechanisms underlying the structural improvement.

  17. Regional distribution of neuropeptide processing endopeptidases in adult rat brain.

    PubMed

    Berman, Y L; Rattan, A K; Carr, K; Devi, L

    1994-01-01

    Many peptide hormone and neuropeptide precursors undergo post-translational processing at mono- and/or dibasic residues. An enzymatic activity capable of processing prodynorphin at a monobasic processing site designated 'dynorphin converting enzyme' has been previously reported in rat rain and bovine pituitary. In this study the distribution of dynorphin converting enzyme activity in ten regions of rat brain has been compared with the distribution of subtilisin-like processing enzymes and with the immuno-reactive dynorphin peptides. The distribution of dynorphin converting enzyme activity generally matches the distribution of immuno-reactive dynorphin B-13 in most but not all brain regions. The regions that are known to have a relatively large number of immuno-reactive dynorphin-neurons also contain high levels of dynorphin converting enzyme activity. The distribution of dynorphin converting enzyme activity does not match the distribution of subtilisin-like processing enzyme or carboxypeptidase E activities. Taken together the data support the possibility that the dynorphin converting enzyme is involved in the maturation of dynorphin, as well as other neuropeptides, and peptide hormones.

  18. Effect of dietary caffeine and theophylline on urinary calcium excretion in the adult rat.

    PubMed

    Whiting, S J; Whitney, H L

    1987-07-01

    The chronic effects of dietary caffeine or theophylline on urinary calcium excretion were investigated in the adult male rat. When caffeine was added at two concentrations, 0.75 and 1.50 g/kg diet, 24-h urinary calcium excretion rose 300 and 450% on d 7, and 200 and 330% on d 14, respectively. There were no changes in the 24-h urinary excretion of phosphate, sulfate, sodium and cAMP nor did urine volume change. The high dose of caffeine was compared to an equimolar dose of theophylline (1.39 g/kg diet) in both Wistar and Sprague-Dawley rats. Urinary calcium excretion in theophylline-treated rats was significantly greater than in caffeine-treated rats on all sampling days and in both strains of rat; the calciuric effect lasted at least 22 d. When rats were given indomethacin (3.3 mg/kg diet) the calciuria induced by caffeine and theophylline was abolished, and sodium excretion in all groups was reduced by 35-50%, but urine volume was unchanged. The calciuria of methylxanthine feeding may result from a prostaglandin-mediated process distinct from diuresis. PMID:3612301

  19. Temporal expression of mutant LRRK2 in adult rats impairs dopamine reuptake.

    PubMed

    Zhou, Hongxia; Huang, Cao; Tong, Jianbin; Hong, Weimin C; Liu, Yong-Jian; Xia, Xu-Gang

    2011-01-01

    Parkinson's disease (PD) results from progressive degeneration of dopaminergic neurons. Most PD cases are sporadic, but some have pathogenic mutation in the individual genes. Mutation of the leucine-rich repeat kinase-2 (LRRK2) gene is associated with familial and sporadic PD, as exemplified by G2019S substitution. While constitutive expression of mutant LRRK2 in transgenic mice fails to induce neuron death, transient expression of the disease gene by viral delivery causes a substantial loss of dopaminergic neurons in mice. To further assess LRRK2 pathogenesis, we created inducible transgenic rats expressing human LRRK2 with G2019S substitution. Temporal overexpression of LRRK2(G2019S) in adult rats impaired dopamine reuptake by dopamine transporter (DAT) and thus enhanced locomotor activity, the phenotypes that were not observed in transgenic rats constitutively expressing the gene throughout life time. Reduced DAT binding activity is an early sign of dopaminergic dysfunction in asymptomatic subjects carrying pathogenic mutation in LRRK2. Our transgenic rats recapitulated the initiation process of dopaminergic dysfunction caused by pathogenic mutation in LRRK2. Inducible transgenic approach uncovered phenotypes that may be obscured by developmental compensation in constitutive transgenic rats. Finding in inducible LRRK2 transgenic rats would guide developing effective strategy in transgenic studies: Inducible expression of transgene may induce greater phenotypes than constitutive gene expression, particularly in rodents with short life time. PMID:21698001

  20. Associative and non-associative blinking in classically conditioned adult rats.

    PubMed

    Lindquist, Derick H; Vogel, Richard W; Steinmetz, Joseph E

    2009-03-01

    Over the last several years, a growing number of investigators have begun using the rat in classical eyeblink conditioning experiments, yet relatively few parametric studies have been done to examine the nature of conditioning in this species. We report here a parametric analysis of classical eyeblink conditioning in the adult rat using two conditioned stimulus (CS) modalities (light or tone) and three interstimulus intervals (ISI; 280, 580, or 880 ms). Rats trained at the shortest ISI generated the highest percentage of conditioned eyeblink responses (CRs) by the end of training. At the two longer ISIs, rats trained with the tone CS produced unusually high CR percentages over the first few acquisition sessions, relative to rats trained with the light CS. Experiment 2 assessed non-associative blink rates in response to presentations of the light or tone, in the absence of the US, at the same ISI durations used in paired conditioning. Significantly more blinks occurred with longer than shorter duration lights or tones. A higher blink rate was also recorded at all three durations during the early tone-alone sessions. The results suggest that early in classical eyeblink conditioning, rats trained with a tone CS may emit a high number of non-associative blinks, thereby inflating the CR frequency reported at this stage of training. PMID:19071146

  1. Micro-CT analysis of myocardial blood supply in young and adult rats

    NASA Astrophysics Data System (ADS)

    Schaefer, Heather M.; Beighley, Patricia E.; Eaker, Diane R.; Vercnocke, Andrew J.; Ritman, Erik L.

    2009-02-01

    This study addresses whether the vasculature grows in proportion to the myocardium as the rat heart develops. The volume of myocardium and coronary vessels were estimated from micro-CT images of the hearts injected with Microfil(R) contrast agent. Young (n=5) and adult (n=5) hearts were scanned, resulting in 3D images comprised of 20μm on-a-side cubic voxels. The myocardial muscle and vessel lumen volumes were measured for all vessels 40 to 320μm in diameter by an erosion and dilation method applied to the binary images in which the contrast in the vessels were assigned "1" and all non-opacified entities were assigned "0". The average total muscle volume increases by 50%, 129.4 to 237.4mm3, from young to adult rats, while the luminal volume increases by 10%, 16.6 to 18.6mm3. The vessel volume is 12% of the total muscle volume in young and 8% in adults. For a given vessel volume, the muscle volume in the young is 82% of the muscle volume in adults. We conclude that as the heart matures, the myocardium grows more rapidly than the vasculature. This may result in greater angles of separation between vessel branches, and the increase in myocardial coronary volume. The ratio suggests either higher blood flow velocity or a lower metabolic rate in adults.

  2. Effect of the antioxidant dibunol on adrenocortical, thyroid, and adenohypopyseal function in adult and old rats

    SciTech Connect

    Gorban', E.N.

    1986-04-01

    This paper studies the effect of dibunol (4-methyl-2,6-di-tert-butylphenol) (D) on the function of the adrenal cortex, thyroid gland, and adenhypophysis, which produces trophic hormones for the other two glands. Experiments were carried out on adult rats. After injection of D concentrations of corticosterone (CS), triodothyronine (T/sub 3/), ACTH, and thyrotrophin (TSH) in the blood plasma and the CS concentration in tssue of the adenohypophysis were determined. It is shown that injection of D caused biphasic changes in the CS concentration in both tissues studied in adult and old animals.

  3. Thermoregulation in rats exposed perinatally to dioxin: core temperature stability to altered ambient temperature, behavioral thermoregulation, and febrile response to lipopolysaccharide.

    PubMed

    Gordon, C J; Miller, D B

    1998-08-21

    Recent studies have shown that perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) alters thermoregulatory function in adult rats and hamsters, indicated by a reduced body temperature during the animal's nocturnal phase. The present study was designed to assess the behavioral thermoregulation, ability to develop a fever, and thermoregulatory stability as a function of ambient temperature (Ta) in rats exposed perinatally to TCDD. Pregnant Long-Evans rats were exposed on gestational day (GD) 15 to 1 microg TCDD/kg (po). The male offspring were implanted with transmitters to monitor core temperature (Tc) and motor activity (MA). The 24-h pattern of core temperature was affected by TCDD exposure, characterized by a reduced nocturnal Tc. At some ages, the diurnal Tc of the TCDD group was elevated. This dysfunction in temperature regulation was most apparent at 7 and 11 mo of age. The 24-h pattern of MA was also altered by TCDD. The hypothermic effects of TCDD were most pronounced at cooler Ta values of 10 to 22 degrees C. In contrast, behavioral thermoregulation, assessed by measuring the selected Ta and Tc of rats in a temperature gradient, was unaffected by TCDD. The ability to develop a fever following administration of lipopolysaccharide (LPS) endotoxin (Escherichia coli; 50 microg/kg) was accentuated in the TCDD-treated animals. The data confirm a nocturnal hypothermia in rats prenatally exposed to TCDD. However, the normal behavioral regulation of Tc suggests that hypothalamic thermoregulatory centers are not permanently altered. The accentuated fever in TCDD animals shows possible functional alterations in the neuroimmune and/or thermoregulatory axes involved in fever. PMID:9726785

  4. Changes in aortic stiffness related to elastic fiber network anomalies in the Brown Norway rat during maturation and aging.

    PubMed

    Osborne-Pellegrin, Mary; Labat, Carlos; Mercier, Nathalie; Challande, Pascal; Lacolley, Patrick

    2010-07-01

    Adult Brown Norway (BN) rats exhibit numerous internal elastic lamina (IEL) ruptures in the abdominal aorta (AA) and a lower aortic elastin-to-collagen ratio (E/C) compared with other strains. We studied here AA mechanical properties in BN compared with control strains. AA stiffness (assessed by plotting elastic modulus/wall-stress curves obtained under anesthesia), thoracic aorta elastin and collagen contents, and IEL ruptures in AA were measured in male BN and LOU rats aged 6, 10, and 15 wk. The Long Evans (LE) control strain was compared with BN at more advanced ages (15, 28, and 64 wk). At all ages, aortic E/C was lower in BN than in control strains. At 6 wk, AA stiffness was greater in BN than in LOU. In both strains, AA stiffness decreased between 6 and 10 wk, more so in BN than in LOU, and then increased, reaching similar values at 15 wk. BN AA stiffness was not different from that of LE at 15 and 28 wk, but was significantly lower at 64 wk. The increased stiffness in young BN rat AA may be due to the decreased E/C. IEL rupture onset in the BN around 7-8 wk, which decreases stiffness, as suggested by its pharmacological modulation, abolished such differences by 15 wk. Thereafter, age-related AA stiffness increased less in BN than in LE, likely due to the numerous IEL ruptures. We conclude that, in the BN rat, the lower E/C and the presence of IEL ruptures have opposing effects on arterial stiffness.

  5. Adolescent social defeat disturbs adult aggression-related impulsivity in wild-type rats.

    PubMed

    Coppens, Caroline M; Coolen, Alex; de Boer, Sietse F; Koolhaas, Jaap M

    2014-10-01

    Adolescence is generally considered as a developmental period during which adverse social experiences may have lasting consequences in terms of an increased vulnerability to affective disorders. This study aimed at determining the individual susceptibility to adolescent social stress using a rat model. We used rats of the Wild-type Groningen strain, which are characterized by a broad variation in adult levels of aggression and impulsivity. We hypothesized that experience of social defeat in adolescence results in heightened aggression and impulsivity levels in adulthood. In contrast to our expectation, adolescent social defeat did not lead to a difference in the average adult level of aggression and impulsivity, but the significant correlation between offensive aggression and impulsivity found in control animals was not present in animals defeated during adolescence.

  6. Some factors influencing cadmium-manganese interaction in adult rats

    SciTech Connect

    Gruden, N.; Matausic, S. )

    1989-07-01

    Recent data show that even a low dose of cadmium (20 {mu}g/day/rat) significantly suppresses manganese transduodenal transport when administered during a three-day period. The inhibitory effect of cadmium upon manganese absorption is enhanced by concurrently administered iron-fortified milk diet. This suggests that the (synergistic) action of cadmium and iron upon manganese and the competition between these (three) ions in the intestine depend on their relative concentrations and affinity for the binding sites within the intestinal mucosa. For this reason the authors considered it worthwhile examining whether this inhibitory effect of cadmium would be affected by simultaneously administered manganese-fortified milk. Since the absorption of heavy metals and, at the same time, the demand for manganese is higher in the young than in the old animals, they also studied how this interaction depends upon the animals' age and sex and whether it is the same in the whole small intestine.

  7. Perfluorooctane sulfonate effects on the reproductive axis in adult male rats.

    PubMed

    López-Doval, S; Salgado, R; Pereiro, N; Moyano, R; Lafuente, A

    2014-10-01

    Perfluorooctane sulfonate (PFOS) is a neurotoxic agent and it can disrupt the endocrine system activity. This work was undertaken to evaluate the possible effects of PFOS exposure on the hypothalamic-pituitary-testicular axis (HPT) in adult male rats, and to evaluate the possible morphological alterations induced by PFOS in the endocrine tissues of this axis. Adult male rats were orally treated with 0.5; 1.0; 3.0 and 6.0 mg of PFOS/kg/day for 28 days. After PFOS exposure, hypothalamic noradrenaline concentration increased in the anterior hypothalamus and in the median eminence, not changing in the mediobasal hypothalamus. PFOS treated rats presented a decrease of the gonadotropin releasing hormone (GnRH) gene expression, increasing the mRNA levels of the luteinizing hormone (LH) in rats treated with all doses administered except with the dose of 6 mg/kg/day. PFOS also induced a raise of the follicle stimulating hormone (FSH) gene expression in the animals exposed to 0.5 and 1.0 mg of PFOS/kg/day. After PFOS exposure, hypothalamic GnRH concentration was modified, LH and testosterone release was inhibited and FSH secretion was stimulated. Moreover, PFOS induced several histopathological alterations in the hypothalamus, pituitary gland and testis. The results obtained in the present study suggest in general terms that PFOS can inhibit the physiological activity of the reproductive axis in adult male rats, which could be explained, at least in part, by the structural alterations showed in the animals exposed to this chemical: very dense chromatin, condensed ribosomes and a loss of the morphology in the hypothalamus; a degeneration of the gonadotrophic cells, as well as a loss and degeneration of the spermatozoids and a very marked edema in the testis.

  8. Airborne particles of the california central valley alter the lungs of healthy adult rats.

    PubMed Central

    Smith, Kevin R; Kim, Seongheon; Recendez, Julian J; Teague, Stephen V; Ménache, Margaret G; Grubbs, David E; Sioutas, Constantinos; Pinkerton, Kent E

    2003-01-01

    Epidemiologic studies have shown that airborne particulate matter (PM) with a mass median aerodynamic diameter < 10 microm (PM10) is associated with an increase in respiratory-related disease. However, there is a growing consensus that particles < 2.5 microm (PM2.5), including many in the ultrafine (< 0.1 microm) size range, may elicit greater adverse effects. PM is a complex mixture of organic and inorganic compounds; however, those components or properties responsible for biologic effects on the respiratory system have yet to be determined. During the fall and winter of 2000-2001, healthy adult Sprague-Dawley rats were exposed in six separate experiments to filtered air or combined fine (PM2.5) and ultrafine portions of ambient PM in Fresno, California, enhanced approximately 20-fold above outdoor levels. The intent of these studies was to determine if concentrated fine/ultrafine fractions of PM are cytotoxic and/or proinflammatory in the lungs of healthy adult rats. Exposures were for 4 hr/day for 3 consecutive days. The mean mass concentration of particles ranged from 190 to 847 microg/m3. PM was enriched primarily with ammonium nitrate, organic and elemental carbon, and metals. Viability of cells recovered by bronchoalveolar lavage (BAL) from rats exposed to concentrated PM was significantly decreased during 4 of 6 weeks, compared with rats exposed to filtered air (p< 0.05). Total numbers of BAL cells were increased during 1 week, and neutrophil numbers were increased during 2 weeks. These observations strongly suggest exposure to enhanced concentrations of ambient fine/ultrafine particles in Fresno is associated with mild, but significant, cellular effects in the lungs of healthy adult rats. PMID:12782490

  9. The effects of undernutrition on connectivity in the cerebellar cortex of adult rats.

    PubMed Central

    Yucel, F; Warren, M A; Gumusburun, E

    1994-01-01

    The effects of a 30 d period of undernutrition, followed in some animals by nutritional rehabilitation, on neuronal connectivity in adult rat cerebellum were investigated using the disector method. There was no significant difference between well fed (719 +/- 74, mean +/- S.E.) and undernourished (709 +/- 53) synapse-to-neuron ratios in 134-d-old rat cerebellar cortex, nor was there a significant difference in synapse-to-neuron ratios between control animals (941 +/- 71) and previously undernourished rats (813 +/- 42) at 175 d of age. However, the age-related changes were significant (P < 0.05) in the controls, but not in the experimental group. It may be that the period of undernutrition caused subtle changes in the rehabilitating group which reduced the capacity for growth seen in well fed, matched control animals. PMID:8157493

  10. Altered hypothalamic-pituitary function in the adult female rat with streptozotocin-induced diabetes.

    PubMed

    Spindler-Vomachka, M; Johnson, D C

    1985-01-01

    Infertility associated with anovulation and loss of regular oestrous cyclicity is a consequence of diabetes mellitus in the rat. In an attempt to define loci of altered function, studies were undertaken to examine various aspects of hypothalamic-pituitary function in rats treated with streptozotocin. Medial basal hypothalamic fragments from adult female diabetic rats contained the same amount of gonadotrophin-releasing hormone but, with depolarization, released slightly but insignificantly (p greater than 0.05) more than did those from control animals. Furthermore, release of luteinizing hormone from pituitaries exposed to hypothalamic gonadotrophin-releasing hormone was not altered by diabetes. Removal of the negative feedback effect of gonadal steroids upon the hypothalamic-pituitary axis produced an increase in luteinizing hormone and follicle stimulating hormone concentrations in the serum of normal rats within 6h (p less than 0.05), whereas 24h were required for similar increases in diabetic rats. However, the same concentrations of gonadotrophins were found in diabetic and control animals 120 h after ovariectomy. The inhibitory action of oestradiol benzoate on the secretion of gonadotrophins was more pronounced in ovariectomized diabetic than in control rats. A 74% depression in serum luteinizing hormone (p less than 0.01) was produced by 0.5 microgram oestradiol benzoate per day in diabetic rats, while 5 micrograms was required in control animals. Similar reductions in follicle stimulating hormone concentrations (50%, p less than 0.05) were obtained by injecting 5 micrograms of the oestrogen into diabetic or 50 micrograms into control rats. Increases in serum prolactin were greater in the control animals however.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Testosterone potentiates the hypoxic ventilatory response of adult male rats subjected to neonatal stress.

    PubMed

    Fournier, Sébastien; Gulemetova, Roumiana; Joseph, Vincent; Kinkead, Richard

    2014-05-01

    Neonatal stress disrupts development of homeostatic systems. During adulthood, male rats subjected to neonatal maternal separation (NMS) are hypertensive and show a larger hypoxic ventilatory response (HVR), with greater respiratory instability during sleep. Neonatal stress also affects sex hormone secretion; hypoxia increases circulating testosterone of NMS (but not control) male rats. Given that these effects of NMS are not observed in females, we tested the hypothesis that testosterone elevation is necessary for the stress-related increase of the HVR in adult male rats. Pups subjected to NMS were placed in an incubator for 3 h per day from postnatal day 3 to 12. Control pups remained undisturbed. Rats were reared until adulthood, and the HVR was measured by plethysmography (fractional inspired O2 = 0.12, for 20 min). We used gonadectomy to evaluate the effects of reducing testosterone on the HVR. Gonadectomy had no effect on the HVR of control animals but reduced that of NMS animals below control levels. Immunohistochemistry was used to quantify androgen receptors in brainstem areas involved in the HVR. Androgen receptor expression was generally greater in NMS rats than in control rats; the most significant increase was noted in the caudal region of the nucleus tractus solitarii. We conclude that the abnormal regulation of testosterone is important in stress-related augmentation of the HVR. The greater number of androgen receptors within the brainstem may explain why NMS rats are more sensitive to testosterone withdrawal. Based on the similarities of the cardiorespiratory phenotype of NMS rats and patients suffering from sleep-disordered breathing, these results provide new insight into its pathophysiology, especially sex-based differences in its prevalence.

  12. Use of the light/dark test for anxiety in adult and adolescent male rats.

    PubMed

    Arrant, Andrew E; Schramm-Sapyta, Nicole L; Kuhn, Cynthia M

    2013-11-01

    The light/dark (LD) test is a commonly used rodent test of unconditioned anxiety-like behavior that is based on an approach/avoidance conflict between the drive to explore novel areas and an aversion to brightly lit, open spaces. We used the LD test to investigate developmental differences in behavior between adolescent (postnatal day (PN) 28-34) and adult (PN67-74) male rats. We investigated whether LD behavioral measures reflect anxiety-like behavior similarly in each age group using factor analysis and multiple regression. These analyses showed that time in the light compartment, percent distance in the light, rearing, and latency to emerge into the light compartment were measures of anxiety-like behavior in each age group, while total distance traveled and distance in the dark compartment provided indices of locomotor activity. We then used these measures to assess developmental differences in baseline LD behavior and the response to anxiogenic drugs. Adolescent rats emerged into the light compartment more quickly than adults and made fewer pokes into the light compartment. These age differences could reflect greater risk taking and less risk assessment in adolescent rats than adults. Adolescent rats were less sensitive than adults to the anxiogenic effects of the benzodiazepine inverse agonist N-methyl-β-carboline-3-carboxamide (FG-7142) and the α₂ adrenergic antagonist yohimbine on anxiety-like behaviors validated by factor analysis, but locomotor variables were similarly affected. These data support the results of the factor analysis and indicate that GABAergic and noradrenergic modulation of LD anxiety-like behavior may be immature during adolescence.

  13. Characterization of motor skill and instrumental learning time scales in a skilled reaching task in rat.

    PubMed

    Buitrago, Manuel M; Ringer, Thomas; Schulz, Jörg B; Dichgans, Johannes; Luft, Andreas R

    2004-12-01

    Successful motor skill learning requires repetitive training interrupted by rest periods. In humans, improvement occurs within and between training sessions reflecting fast and slow components of motor learning [Karni A, Meyer G, Rey-Hipolito C, Jezzard P, Adams MM, Turner R, et al. The acquisition of skilled motor performance: fast and slow experience-driven changes in primary motor cortex. Proc Natl Acad Sci USA 1998;95:861-8]. Here, these components are characterized in male and female rats using a model of skilled forelimb reaching and are compared to time scales of instrumental learning. Twenty female and 14 male adult Long-Evans rats were pre-trained to operate a motorized door (via a sensor in the opposite cage wall) to access a food pellet by tongue. Latencies between pellet removal and door opening were recorded as measures of instrumental learning. After criterion performance was achieved, skilled forelimb reaching was requested by increasing the pellet-window distance to 1.5cm. Reaching success was recorded per trial. Mean latencies decreased exponentially over sessions and no improvement within-session was found. Skill learning over eight training sessions followed an exponential course in females and a sigmoid course in males. Females acquired the skill significantly faster than males starting at higher baseline levels (P < 0.001) but reaching similar plateaus. Within-session improvement was found during the sessions 1-3 in females and 1-4 in males. Performance at the end of session 1 was not carried over to session 2. Learning curves of individual animals were highly variable. These findings confirm in rat that motor skill learning has fast and slow components. No within-session improvement is seen in instrumental learning.

  14. Factors influencing adverse skin responses in rats receiving repeated subcutaneous injections and potential impact on neurobehavior

    PubMed Central

    Levoe, S. Nikki; Flannery, Brenna M.; Brignolo, Laurie; Imai, Denise M.; Koehne, Amanda; Austin, Adam T.; Bruun, Donald A.; Tancredi, Daniel J.; Lein, Pamela J.

    2015-01-01

    Repeated subcutaneous (s.c.) injection is a common route of administration in chronic studies of neuroactive compounds. However, in a pilot study we noted a significant incidence of skin abnormalities in adult male Long-Evans rats receiving daily s.c. injections of peanut oil (1.0 ml/kg) in the subscapular region for 21 d. Histopathological analyses of the lesions were consistent with a foreign body reaction. Subsequent studies were conducted to determine factors that influenced the incidence or severity of skin abnormalities, and whether these adverse skin reactions influenced a specific neurobehavioral outcome. Rats injected daily for 21 d with food grade peanut oil had an earlier onset and greater incidence of skin abnormalities relative to rats receiving an equal volume (1.0 ml/kg/d) of reagent grade peanut oil or triglyceride of coconut oil. Skin abnormalities in animals injected daily with peanut oil were increased in animals housed on corncob versus paper bedding. Comparison of animals obtained from different barrier facilities exposed to the same injection paradigm (reagent grade peanut oil, 1.0 ml/kg/d s.c.) revealed significant differences in the severity of skin abnormalities. However, animals from different barrier facilities did not perform differently in a Pavlovian fear conditioning task. Collectively, these data suggest that environmental factors influence the incidence and severity of skin abnormalities following repeated s.c. injections, but that these adverse skin responses do not significantly influence performance in at least one test of learning and memory. PMID:25705100

  15. Interaction of ambient temperature and microwave power density on schedule-controlled behavior in the rat

    NASA Astrophysics Data System (ADS)

    Gage, Michael I.; Mark Guyer, W.

    1982-01-01

    Most guidelines of microwave exposure do not explicitly address effects of ambient temperature. Our experiment revealed that ambient temperature potentiates the behavioral effects of intensity of irradiation. Sixty-four adult male Long-Evans rats were trained to insert their heads into a food cup to obtain food pellets on a 1-min variable-interval schedule of reinforcement. Two groups of four rats each were then exposed to 2450-MHz CW microwaves for 15.5 hours under one of the following eight combinations of power density and air temperature: 8 or 14 mW/cm2 at 22°C 0, 8, or 14 mW/cm2 at 26°C and 0, 8, or 14 mW/cm2 at 30°C (relative humidity was 50% in all cases). Response rate of each rat following exposure was compared with its control rate at 0 mW/cm2 and 22°C. After exposure at 8 mW/cm2, response rates were reduced by a mean of 13.8% at 22°C, 27.5Percnt; at 26°C, and 77.5% at 30°C. After exposure at 14 mW/cm2, rates were reduced by a mean of 21.1% at 22°C, 43.7% at 26°C, and 80.0% at 30°C. In the absence of microwaves the higher temperatures caused only slight decreases in response rate.

  16. Selective immunolesions of CH4 cholinergic neurons do not disrupt spatial memory in rats.

    PubMed

    Galani, Rodrigue; Lehmann, Olivia; Bolmont, Tristan; Aloy, Elizabeth; Bertrand, Fabrice; Lazarus, Christine; Jeltsch, Hélène; Cassel, Jean-Christophe

    2002-05-01

    Adult male Long-Evans rats were subjected to bilateral lesions of the cholinergic neurons in the nucleus basalis magnocellularis (NBM) by injection of 0.2 or 0.4 microg 192-IgG-saporin in 0.4 microl phosphate-buffered saline. Control rats received an equivalent amount of phosphate-buffered saline. Starting 2 weeks after surgery, all rats were tested for locomotor activity in their home cage, beam-walking performance, T-maze alternation rates (working memory), reference and working memory performance in a water-maze task, and memory capabilities in the eight-arm radial maze task using uninterrupted and interrupted (delay of 2 min, 2 h and 6 h after four arms had been visited) testing procedures. Histochemical analysis showed a significant decrease of acetylcholinesterase (AChE)-positive reaction products (30-66%) in various cortical regions at the 0.2-microg dose. At the dose of 0.4 microg, there was an additional, although weak, damage to the hippocampus (17-30%) and the cingulate cortex (34%). The behavioral results showed only minor impairments in spatial memory tasks, and only during initial phases of the tests (reference memory in the water maze, working memory in the radial maze). The behavioral effects of the dramatic cholinergic lesions do not support the idea of a substantial implication of cholinergic projections from the NBM to the cortex in the memory processes assessed in this study, but they remain congruent with an involvement of these projections in attentional functions. PMID:12175591

  17. Reproductive toxicity of a single dose of 1,3-dinitrobenzene in two ages of young adult male rats

    EPA Science Inventory

    These studies evaluated the reproductive response and the possible influence of testicular maturation on the reproductive parameters, in male rats treated with 1,3-dinitrobenzene (m-DNB). Young adult male rats (75 or 105 days of age) were given a single oral dose of 0, 8, 16, 24,...

  18. Effects of estradiol and methoxychlor on Leydig cell regeneration in the adult rat testis.

    PubMed

    Chen, Bingbing; Chen, Dongxin; Jiang, Zheli; Li, Jingyang; Liu, Shiwen; Dong, Yaoyao; Yao, Wenwen; Akingbemi, Benson; Ge, Renshan; Li, Xiaokun

    2014-05-06

    The objective of the present study is to determine whether methoxychlor (MXC) exposure in adulthood affects rat Leydig cell regeneration and to compare its effects with estradiol (E2). Adult 90-day-old male Sprague-Dawley rats received ethane dimethane sulfonate (EDS) to eliminate the adult Leydig cell population. Subsequently, rats were randomly assigned to four groups and gavaged with corn oil (control), 0.25 mg/kg E2 and 10 or 100 mg/kg MXC daily from days 5 to 30 post-EDS treatment. The results showed that MXC and E2 reduced serum testosterone levels on day 58 post-EDS treatment. qPCR showed Hsd17b3 mRNA levels were downregulated 7-15 fold by E2 and MXC, indicating that development of the new population of Leydig cells was arrested at the earlier stage. This observation was supported by the results of histochemical staining, which demonstrated that Leydig cells in MXC-treated testis on day 58 post-EDS treatment were mostly progenitor Leydig cells. However, Pdgfb mRNA levels were downregulated, while Lif transcript levels were increased by MXC. In contrast, E2 did not affect gene expression for these growth factors. In conclusion, our findings indicated that both MXC and E2 delayed rat Leydig cell regeneration in the EDS-treated model, presumably acting by different mechanisms.

  19. Effects of Estradiol and Methoxychlor on Leydig Cell Regeneration in the Adult Rat Testis

    PubMed Central

    Chen, Bingbing; Chen, Dongxin; Jiang, Zheli; Li, Jingyang; Liu, Shiwen; Dong, Yaoyao; Yao, Wenwen; Akingbemi, Benson; Ge, Renshan; Li, Xiaokun

    2014-01-01

    The objective of the present study is to determine whether methoxychlor (MXC) exposure in adulthood affects rat Leydig cell regeneration and to compare its effects with estradiol (E2). Adult 90-day-old male Sprague-Dawley rats received ethane dimethane sulfonate (EDS) to eliminate the adult Leydig cell population. Subsequently, rats were randomly assigned to four groups and gavaged with corn oil (control), 0.25 mg/kg E2 and 10 or 100 mg/kg MXC daily from days 5 to 30 post-EDS treatment. The results showed that MXC and E2 reduced serum testosterone levels on day 58 post-EDS treatment. qPCR showed Hsd17b3 mRNA levels were downregulated 7–15 fold by E2 and MXC, indicating that development of the new population of Leydig cells was arrested at the earlier stage. This observation was supported by the results of histochemical staining, which demonstrated that Leydig cells in MXC-treated testis on day 58 post-EDS treatment were mostly progenitor Leydig cells. However, Pdgfb mRNA levels were downregulated, while Lif transcript levels were increased by MXC. In contrast, E2 did not affect gene expression for these growth factors. In conclusion, our findings indicated that both MXC and E2 delayed rat Leydig cell regeneration in the EDS-treated model, presumably acting by different mechanisms. PMID:24806340

  20. Neonatal Maternal Separation Augments Carotid Body Response to Hypoxia in Adult Males but Not Female Rats

    PubMed Central

    Soliz, Jorge; Tam, Rose; Kinkead, Richard

    2016-01-01

    Perinatal exposure to adverse experiences disrupts brain development, including the brainstem network that regulates breathing. At adulthood, rats previously subjected to stress (in the form of neonatal maternal separation; NMS) display features reported in patients suffering from sleep disordered breathing, including an increased hypoxic ventilatory response and hypertension. This effect is also sex-specific (males only). Based on these observations, we hypothesized that NMS augments the carotid body's O2-chemosensitivity. Using an isolated and perfused ex vivo carotid body preparation from adult rats we compared carotid sinus nerve (CSN) responses to hypoxia and hypercapnia in carotid bodies harvested from adult rats that either experienced control conditions (no experimental manipulation) or were subjected to NMS (3 h/day from postnatal days 3 to 12). In males, the CSN response to hypoxia measured in preparations from NMS males was 1.5 fold higher than controls. In control rats, the female's response was similar to that of males; however, the increase in CSN activity measured in NMS females was 3.0 times lower than controls. The CSN response to hypercapnia was not influenced by stress or sex. We conclude that NMS is sufficient to have persistent and sex-specific effects on the carotid body's response to hypoxia. Because NMS also has sex-specific effects on the neuroendocrine response to stress, we propose that carotid body function is influenced by stress hormones. This, in turn, leads to a predisposition toward cardio-respiratory disorders. PMID:27729873

  1. Perinatal thiamine restriction affects central GABA and glutamate concentrations and motor behavior of adult rat offspring.

    PubMed

    Ferreira-Vieira, Talita Hélen; de Freitas-Silva, Danielle Marra; Ribeiro, Andrea Frozino; Pereira, Sílvia Rejane Castanheira; Ribeiro, Ângela Maria

    2016-03-23

    The purposes of the present study were to investigate the effects of perinatal thiamine deficiency, from the 11th day of gestation until the 5th day of lactation, on motor behavior and neurochemical parameters in adult rat offspring, using 3-month-old, adult, male Wistar rats. All rats were submitted to motor tests, using the rotarod and paw print tasks. After behavioral tests, their thalamus, cerebellum and spinal cord were dissected for glutamate and GABA quantifications by high performance liquid chromatography. The thiamine-restricted mothers (RM) group showed a significant reduction of time spent on the rotarod at 25 rpm and an increase in hind-base width. A significant decrease of glutamate concentration in the cerebellum and an increase of GABA concentrations in the thalamus were also observed. For the offspring from control mothers (CM) group there were significant correlations between thalamic GABA concentrations and both rotarod performance and average hind-base width. In addition, for rats from the RM group a significant correlation between stride length and cerebellar GABA concentration was found. These results show that the deficiency of thiamine during an early developmental period affects certain motor behavior parameters and GABA and glutamate levels in specific brain areas. Hence, a thiamine deficiency episode during an early developmental period can induce motor impairments and excitatory and inhibitory neurotransmitter changes that are persistent and detectable in later periods of life. PMID:26836141

  2. Impaired acclimatization to chronic hypoxia in adult male and female rats following neonatal hypoxia.

    PubMed

    Lumbroso, Delphine; Joseph, Vincent

    2009-08-01

    We tested the hypothesis that neonatal exposure to hypoxia alters acclimatization to chronic hypoxia later in life. Rat pups were exposed to normobaric hypoxia (12% O(2); nHx group) in a sealed chamber, or to normoxia (21% O(2); nNx group) from the day before birth to postnatal day 10. The animals were then raised in normal conditions until reaching 12 wk of age. At this age, we assessed ventilatory and hematological acclimatization to chronic hypoxia by exposing male and female nHx and nNx rats for 2 wk to 10% O(2). Minute ventilation, metabolic rate, hypoxic ventilatory response, hematocrit, and hemoglobin levels were measured both before and after acclimatization. We also quantified right ventricular hypertrophy as an index of pulmonary hypertension both before and after acclimatization. There was a significant effect of neonatal hypoxia that decreases ventilatory response (relative to metabolic rate, VE/VCO(2)) to acute hypoxia before acclimatization in males but not in females. nHx rats had an impaired acclimatization to chronic hypoxia characterized by altered respiratory pattern and elevated hematocrit and hemoglobin levels after acclimatization, in both males and females. Right ventricular hypertrophy was present before and after acclimatization in nHx rats, indicating that neonatal hypoxia results in pulmonary hypertension in adults. We conclude that neonatal hypoxia impairs acclimatization to chronic hypoxia in adults and may be a factor contributing to the establishment of chronic mountain sickness in humans living at high altitude.

  3. Basic fibroblast growth factor protects against excitotoxicity and chemical hypoxia in both neonatal and adult rats.

    PubMed

    Kirschner, P B; Henshaw, R; Weise, J; Trubetskoy, V; Finklestein, S; Schulz, J B; Beal, M F

    1995-07-01

    Basic fibroblast growth factor (bFGF) is a polypeptide growth factor that promotes neuronal survival. We recently found that systemic administration of bFGF protects against both excitotoxicity and hypoxia-ischemia in neonatal animals. In the present study, we examined whether systemically administered bFGF could prevent neuronal death induced by intrastriatal injection of N-methyl-D-aspartate (NMDA) or chemical hypoxia induced by intrastriatal injection of malonate in adult rats and 1-methyl-4-phenylpyridinium (MPP+) in neonatal rats. Systemic administration of bFGF (100 micrograms/kg) for three doses both before and after intrastriatal injection of either NMDA or malonate in adult rats produced a significant neuroprotective effect. In neonatal rats, bFGF produced dose-dependent significant neuroprotective effects against MPP+ neurotoxicity, with a maximal protection of approximately 50% seen with either a single dose of bFGF of 300 micrograms/kg or three doses of 100 micrograms/kg. These results show that systemic administration of bFGF is effective in preventing neuronal injury under circumstances in which the blood-brain barrier may be compromised, raising the possibility that this strategy could be effective in stroke.

  4. A spaceflight study of synaptic plasticity in adult rat vestibular maculas

    NASA Technical Reports Server (NTRS)

    Ross, M. D.

    1994-01-01

    Behavioral signs of vestibular perturbation in altered gravity have not been well correlated with structural modifications in neurovestibular centers. This ultrastructural research investigated synaptic plasticity in hair cells of adult rat utricular maculas exposed to microgravity for nine days on a space shuttle. The hypothesis was that synaptic plasticity would be more evident in type II hair cells because they are part of a distributed modifying macular circuitry. All rats were shared with other investigators and were subjected to treatments unrelated to this experiment. Maculas were obtained from flight and control rats after shuttle return (R + 0) and nine days post-flight (R + 9). R + 9 rats had chromodacryorrhea, a sign of acute stress. Tissues were prepared for ultrastructural study by conventional methods. Ribbon synapses were counted in fifty serial sections from medial utricular macular regions of three rats of each flight and control group. Counts in fifty additional consecutive sections from one sample in each group established method reliability. All synapses were photographed and located to specific cells on mosaics of entire sections. Pooled data were analyzed statistically. Flown rats showed abnormal posture and movement at R + 0. They had statistically significant increases in total ribbon synapses and in sphere-like ribbons in both kinds of hair cells; in type II cells, pairs of synapses nearly doubled and clusters of 3 to 6 synapses increased twelve-fold. At R + 9, behavioral signs were normal. However, synapse counts remained high in both kinds of hair cells of flight maculas and were elevated in control type II cells. Only counts in type I cells showed statistically significant differences at R + 9. High synaptic counts at R + 9 may have resulted from stress due to experimental treatments. The results nevertheless demonstrate that adult maculas retain the potential for synaptic plasticity. Type II cells exhibited more synaptic plasticity, but

  5. Hyperforin alleviates mood deficits of adult rats suffered from early separation.

    PubMed

    Zhu, Minghui; Liu, Chunhua; Qin, Xuan; Yang, Zhuo

    2015-11-01

    In this study, we aimed to explore the effect of hyperforin (Hyp) on adult rats suffered from early separation. Wistar infant rats were randomly divided into three groups: control group (CON), early separation from parents group (ESP), and early separation from parents+treatment with 3mg/kg/day Hyp group (ESP+Hyp). Postnatal rats of ESP group and ESP+Hyp group were separated from their mothers for 6h every day on the 14th day after birth, and this separation lasted for 3 weeks, while rats of CON group had no separation. Hyperforin was intragastric administrated on the 21th day after birth, and lasted for 2 weeks in ESP+Hyp group. After separation, adult rats were evaluated by using the open field test (OFT), novelty suppressed feeding test (NSF) and forced swimming test (FST). In OFT, time spent in central grids was much shorter in ESP group compared with that of CON group. After treatment with hyperforin, time spent in central area was much longer compared with that of ESP group. In NSF, the feeding latency of ESP group was much longer than that of CON group. After treatment with hyperforin, the feeding latency was shorter compared with that of ESP group. In FST, score of ESP group was markedly higher than that of CON group. Interestingly, the score was obviously lower in ESP+Hyp group than that of ESP group. In conclusion, these results suggest that hyperforin is able to alleviate anxiety and remit depression in ESP rats. PMID:26420027

  6. A new protocol for cultivation of predegenerated adult rat Schwann cells.

    PubMed

    Pietrucha-Dutczakv, Marita; Marcol, Wiesław; Francuz, Tomasz; Gołka, Dariusz; Lewin-Kowalik, Joanna

    2014-09-01

    The purpose of this study was to optimize the methodology of cultivation of predegenerated Schwann cells (SCs). SCs were isolated from 7-day-predegenerated sciatic nerves of adult rats. We applied commercially available culture medium for cultivation of endothelial cells endothelial cell culture medium (EBM-2) instead of Dulbecco's Modified Eagle's Medium commonly used to culture adult Schwann cells. Additionally, cell culture medium was supplemented with factors specifically supporting SCs growth as: bovine pituitary extract (5 μg/ml), heregulin (40 ng/ml) and insulin (2.5 ng/ml). Similarly to the reports of others authors, we did not observe any beneficial effects of Forskolin application, so we didn't supplement our medium with it. Cell culture purity was determined by counting the ratio of GFAP, N-Cadherin and NGFR p75-positive cells to total number of cells. About 94-97 % of cells were confirmed as Schwann cells. As a result, we obtained sufficient number and purity of Schwann cells to be applied in different experimental models in rats. EBM-2 medium coated with fibronectin was the best for cultivation of adult rat Schwann cells.

  7. Caffeine in the neonatal period induces long-lasting changes in sleep and breathing in adult rats.

    PubMed

    Montandon, Gaspard; Horner, Richard L; Kinkead, Richard; Bairam, Aida

    2009-11-15

    Caffeine is commonly used clinically to treat apnoeas and unstable breathing associated with premature birth. Caffeine antagonizes adenosine receptors and acts as an efficient respiratory stimulant in neonates. Owing to its persistent effects on adenosine receptor expression in the brain, neonatal caffeine administration also has significant effects on maturation of the respiratory control system. However, since adenosine receptors are critically involved in sleep regulation, and sleep also modulates breathing, we tested the hypothesis that neonatal caffeine treatment disrupts regulation of sleep and breathing in the adult rat. Neonatal caffeine treatment (15 mg kg(-1) day(-1)) was administered from postnatal days 3-12. At adulthood (8-10 weeks old), sleep and breathing were measured with a telemetry system and whole-body plethysmography respectively. In adult rats treated with caffeine during the neonatal period, sleep time was reduced, sleep onset latency was increased, and non-rapid eye movement (non-REM) sleep was fragmented compared to controls. Ventilation at rest was higher in caffeine-treated adult rats compared to controls across sleep/wake states. Hypercapnic ventilatory responses were significantly reduced in caffeine-treated rats compared to control rats across sleep/wake states. Additional experiments in adult anaesthetized rats showed that at similar levels of arterial blood gases, phrenic nerve activity was enhanced in caffeine-treated rats. This study demonstrates that administration of caffeine in the neonatal period alters respiratory control system activity in awake and sleeping rats, as well as in the anaesthetized rats, and also has persistent disrupting effects on sleep that are apparent in adult rats.

  8. Brain Pathology in Adult Rats Treated With Domoic Acid.

    PubMed

    Vieira, A C; Alemañ, N; Cifuentes, J M; Bermúdez, R; Peña, M López; Botana, L M

    2015-11-01

    Domoic acid (DA) is a neurotoxin reported to produce damage to the hippocampus, which plays an important role in memory. The authors inoculated rats intraperitoneally with an effective toxic dose of DA to study the distribution of the toxin in major internal organs by using immunohistochemistry, as well as to evaluate the induced pathology by means of histopathologic and immunohistochemical methods at different time points after toxin administration (6, 10, and 24 hours; 5 and 54 days). DA was detected by immunohistochemistry exclusively in pyramidal neurons of the hippocampus at 6 and 10 hours after dosing. Lesions induced by DA were prominent at 5 days following treatment in selected regions of the brain: hippocampus, amygdala, piriform and perirhinal cortices, olfactory tubercle, septal nuclei, and thalamus. The authors found 2 types of lesions: delayed death of selective neurons and large areas of necrosis, both accompanied by astrocytosis and microgliosis. At 54 days after DA exposure, the pathology was characterized by still-distinguishable dying neurons, calcified lesions in the thalamus, persistent astrocytosis, and pronounced microgliosis. The expression of nitric oxide synthases suggests a role for nitric oxide in the pathogenesis of neuronal degeneration and chronic inflammation induced by DA in the brain.

  9. CYTOPLASMIC INCLUSIONS RESEMBLING NUCLEOLI IN SYMPATHETIC NEURONS OF ADULT RATS

    PubMed Central

    Grillo, Mary A.

    1970-01-01

    A distinctive cytoplasmic inclusion consisting of a convoluted network of electron-opaque strands embedded in a less dense matrix was identified in the neurons, but not in the supporting cells, of rat sympathetic ganglia. This ball-like structure, designated "nematosome," measures ∼ 0.9 µ and lacks a limiting membrane. Its strands (diameter = 400–600 A) appear to be made of an entanglement of tightly packed filaments and particles ∼ 25–50 A thick. Cytochemical studies carried out with the light microscope suggest the presence of nonhistone proteins and some RNA. Usually only one such structure is present in a cell, and it appears to occur in most ganglion cells. Although they can be seen anywhere in the cell body, nematosomes are typically located in the perinuclear cytoplasm, where they are often associated with smooth-surfaced and coated vesicles. In fine structure and stainability, they bear a resemblance to the fibrous component of the nucleolus. Subsynaptic formations, which are a special feature of some of the synapses in sympathetic ganglia, appear similar to the threadlike elements in the nematosomes. The possibility that these three structures—nucleolus, nematosome, and subsynaptic formation—may be interrelated in origin and function is discussed. PMID:5458990

  10. Behavioral deficits in adult rats treated neonatally with glutamate.

    PubMed

    Hlinák, Zdenek; Gandalovicová, Dana; Krejcí, Ivan

    2005-01-01

    The present study evaluated long-term behavioral consequences of neonatal monosodium-l-glutamate (MSG) treatment in rats. The pups received MSG (3 mg/g sc) daily from postnatal day (PD) 5-12. Data from an automatic activity monitor showed that locomotion of MSG-treated females and males aged 56 and 84 days was significantly reduced. Beginning PD 120, three behavioral tests were performed. As compared to the controls, in the elevated plus maze test, modified to evaluate the adaptive form of spatial memory, MSG-treated animals of both sex had significantly prolonged start and transfer latencies. In the social recognition test, assessing olfactory working memory, MSG-treated males displayed a reduced interest in the juvenile conspecific as the stimulus partner during both the initial exposure and re-exposure performed 30 min later. In the open field test, a significant decrease in the habituation rate was found in MSG-treated animals. Sex-dependent differences in behavioral performance were suggested in the open field and elevated plus maze tests. Behavioral changes are discussed in light of the deficits in perception and processing of visual and olfactory stimuli.

  11. Disordered food intake and obesity in rats lacking cholecystokinin A receptors.

    PubMed

    Moran, T H; Katz, L F; Plata-Salaman, C R; Schwartz, G J

    1998-03-01

    Otsuka Long-Evans Tokushima Fatty (OLETF) rats develop obesity, hyperglycemia, and non-insulin-dependent diabetes mellitus and do not express cholecystokinin A (CCK-A) receptors, the receptor subtype mediating the satiety actions of CCK. In short-term feeding tests, male OLETF rats were completely resistant to exogenous CCK, and their response to bombesin was attenuated. Comparisons of liquid meal consumption in OLETF and control Long-Evans Tokushima (LETO) rats demonstrated that 1) OLETF rats had greater intakes during 30-min scheduled daytime meals and significantly larger and fewer spontaneous night-time meals and 2) although the initial rates of licking were the same, OLETF rats maintained the initial rate longer and the rate at which their licking declined was slower. In 24-h solid food access tests, OLETF rats consumed significantly more pellets than LETO controls, and this increase was attributable to significant increases in meal size. Together, these data are consistent with the interpretation that the lack of CCK-A receptors in OLETF rats results in a satiety deficit leading to increases in meal size, overall hyperphagia, and obesity.

  12. Hypoglycemic activity of Eriobotrya japonica seeds in type 2 diabetic rats and mice.

    PubMed

    Tanaka, Kazunari; Nishizono, Shoko; Makino, Nozomi; Tamaru, Shizuka; Terai, Osamu; Ikeda, Ikuo

    2008-03-01

    The hypoglycemic effects of Eriobotrya japonica seeds were investigated in type 2 diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats and KK-A(y) mice. The rats and mice were fed on a diet containing 10% powdered Eriobotrya japonica seeds with the coat intact for 4 months. Although the blood glucose concentration in the OLETF rats fed on the control diet without Eriobotrya japonica seeds was increased with time, the concentration in the OLETF rats fed on the diet with Eriobotrya japonica seeds was consistently low throughout the experimental period and was comparable to the level in Long-Evans Tokushima Otsuka (LETO) rats which are normal non-diabetic rats. Serum insulin was significantly lower in the OLETF rats fed on the Eriobotrya japonica seed diet than in those fed on the control diet at the termination of the experimental period. Eriobotrya japonica seeds suppressed the increment of blood glucose for 4 months and also effectively improved the glucose tolerance in the KK-A(y) mice, these actions being mainly exerted by the ethanol extract of the seeds. These results suggest that Eriobotrya japonica seeds had a hypoglycemic property and the effect is attributable to the components extracted by ethanol.

  13. Chronic systemic administration of 5-HT produces weight loss in mature adult male rats.

    PubMed

    Edwards, S

    1995-09-01

    Adult male rats were allowed to free-feed until their body weights had stabilised. They were next trained onto a 4 h per day feeding regimen, until further stabilisation occurred. All rats then received saline injections for 5 days, to establish baseline body weights. One group was then injected with 5.0 mg/kg 5-HT daily for 30 days while the other group continued with saline. Progressive and significant weight loss occurred in the drug-treated animals. After 30 days, the 5-HT-treated rats had lost 7.0% of their baseline body weights, whereas the control group had gained 1.3%. At this point, the 5-HT treated rats were switched back to saline injections to investigate rebound effects. Although the group that had received 5-HT treatment showed evidence of rebound weight gain, mean weights at the end of the 10 day rebound period were still 4.5% lower than baseline values. These data clearly indicate that chronic systemic administration of 5-HT can produce considerable weight loss in rats.

  14. Effect of restraint and copper deficiency on blood pressure and mortality of adult rats

    SciTech Connect

    Klevay, L.M.; Halas, E.S. )

    1989-02-01

    The etiology of most hypertension is unknown; stress is thought to elevate blood pressure. Male, weanling Sprague-Dawley rats were fed a purified diet plus a drinking solution containing 10{mu}g Zn and 2{mu}g Cu/ml (acetate sulfate, respectively). Systolic blood pressure was measured without anesthesia. After being matched by mean weight (280g) and blood pressure into 4 groups of 15, groups 1 and 2 received a drinking solution without copper. After 24 days rats in groups 2 and 4 were restrained for 45 min. daily (A.M.) for 23 days in a small plastic cage (19{times}6{times}6 cm). Final pressures were affected both by stress and dietary Cu: group 1, 119; group 2, 131; group 3, 114; group 4, 123 mm Hg. One rat in each of groups 1, 3, 4 and 10 rats in group 2, died. Among these latter hemorrhage was prominent, blood being found in bladder (2), gut (2), peritoneum (2) and scrotum (1). Copper deficiency decreased cooper in both adrenal gland and liver by 58% and in heart by 29% restraint was without effect. Cardiac sodium was increased 6% only by deficiency. Results confirm the hypertensive effect of copper deficiency in adult rats and reveal that the stress of restraint increases blood pressure. Copper deficiency plus stress is harmful.

  15. γ/δ Cells in Fetal, Neonatal, and Adult Rat Lymphoid Organs

    PubMed Central

    Kühnlein, P.; Vicente, A.; Varas, A.; Hünig, T.

    1995-01-01

    In the present study, we have analyzed the appearance and maturation of γ/δ T cells, recognized with a new mAb V65, in the central and peripheral lymphoid organs of fetal, neonatal, and adult Wistar rats. Cytofluorometrical analysis demonstrated the first V65+ γ/δ T cells in the thymus of 16-17-day embryonic rats, although by immunohistology, they were identified only in 19-day rat embryos in both the cortico-medullary border and thymic medulla. Phenotypically, γ/δ thymocytes from fetal and neonatal thymus expressed CD3, CD2, and CD5, but only 60-80% were CD8+ and approximately 40-50% expressed the α chain (p55) of the IL-2R. In the periphery, the immunohistological study identified for the first time ,γ/δ T cells in the splenic white pulp and the gut of 21-day fetal rats, where they occurred within the epithelium as well as in the lamina propria. After birth, γ/δ lymphocytes appeared in the skin, where they were present as dendritic epidermal T cells in increasing numbers during postnatal life. Whereas these γ/δ T cells formed the predominant T-cell population in the rat skin, γ/δ T cells in peripheral lymphoid organs, BALT, or the gut only represented a minor T-cell population. These results are discussed in comparison to γ/δ T cells of other vertebrate species. PMID:8770557

  16. Myocardial infarction induces cognitive impairment by increasing the production of hydrogen peroxide in adult rat hippocampus.

    PubMed

    Liu, Chunhua; Liu, Ye; Yang, Zhuo

    2014-02-01

    Accumulating clinical evidence has shown a causal relationship between heart diseases and cognitive impairment in clinical, but the underlying mechanism remains unclear. In this study, rats with myocardial infarction (MI) were used to investigate cognition-related synaptic function and proteins. Adult male Wistar rats were subjected to MI by ligating of left anterior descending artery (LAD) and the infarct size of rat heart was measured by 2,3,5-triphenyltetrazoium chloride (TTC) staining. In this study, results showed that compared with control group, long-term potentiation was suppressed in dentate gyrus area, the contents of hydrogen peroxide (H2O2) and malondialdehyde were significantly increased, whereas the Cu/Zn-superoxide dismutase activity and N-methyl-d-aspartate receptor subunit 2B were attenuated in hippocampus of MI rats. Interestingly, it was observed that the PI3K/Akt pathway was activated in MI rats. Therefore, this study suggests that H2O2 plays an important role in cognitive dysfunction induced by MI.

  17. Early deprivation reduced anxiety and enhanced memory in adult male rats.

    PubMed

    Zhang, Xuliang; Wang, Bo; Jin, Jing; An, Shuming; Zeng, Qingwen; Duan, Yanhong; Yang, Liguo; Ma, Jing; Cao, Xiaohua

    2014-09-01

    The effects of early deprivation (ED, which involves both dam and littermate deprivation) on anxiety and memory are less investigated in comparison with maternal separation (MS), and it is not yet clear how ED affects long-term potentiation (LTP) in the hippocampal Schaffer collateral pathway. By using a series of behavioral tests, enzyme-linked immunosorbent assay and field potential recording, we explored the effect of pre-weaning daily 3-h ED on anxiety, memory and potential mechanisms in adult male rats. Compared with control, ED rats spent longer time in open arms of elevated plus maze and in light compartment of light-dark transition box. Consistently, stress-induced blood plasma corticosterone level was also lower in ED rats. Moreover, ED rats showed better performance in social recognition and Morris water maze test. In accordance with results in memory tests, the threshold of LTP induction in hippocampal CA3-CA1 pathway of ED rats was also reduced. Our results indicate ED reduced anxiety, but enhanced social recognition and spatial reference memory. We suggest the diminished hypothalamic-pituitary-adrenal axis response and facilitated hippocampal LTP may contribute to the anxiety-reducing and memory-enhancing effects of ED, respectively.

  18. Hair cell counts in a rat model of sound damage: Effects of tissue preparation & identification of regions of hair cell loss.

    PubMed

    Neal, Christopher; Kennon-McGill, Stefanie; Freemyer, Andrea; Shum, Axel; Staecker, Hinrich; Durham, Dianne

    2015-10-01

    Exposure to intense sound can damage or kill cochlear hair cells (HC). This loss of input typically manifests as noise induced hearing loss, but it can also be involved in the initiation of other auditory disorders such as tinnitus or hyperacusis. In this study we quantify changes in HC number following exposure to one of four sound damage paradigms. We exposed adult, anesthetized Long-Evans rats to a unilateral 16 kHz pure tone that varied in intensity (114 dB or 118 dB) and duration (1, 2, or 4 h) and sacrificed animals 2-4 weeks later. We compared two different methods of tissue preparation, plastic embedding/sectioning and whole mount dissection, for quantifying hair cell loss as a function of frequency. We found that the two methods of tissue preparation produced largely comparable cochleograms, with whole mount dissections allowing a more rapid evaluation of hair cell number. Both inner and outer hair cell loss was observed throughout the length of the cochlea irrespective of sound damage paradigm. Inner HC loss was either equal to or greater than outer HC loss. Increasing the duration of sound exposures resulted in more severe HC loss, which included all HC lesions observed in an analogous shorter duration exposure.

  19. Alcohol self-administration by rats in the presence of a tangible object.

    PubMed

    Files, Forrest J; Meyer, Alexander; Cantz, Paul; Young, Melissa; Sierra, Gabriela; Berman, Dara; Stachelski, April; Cantz, Vanessa

    2006-04-01

    The authors used the sucrose-substitution procedure to train operant self-administration of a 10% alcohol solution in 8 Long-Evans rats. After they established stable responding, they began a 10-session baseline. A 10-session experimental phase followed the baseline phase. During the experimental phase, the authors placed a large glass marble in the center of the experimental chambers before self-administration sessions. The presence of the marble decreased the rats' responding and alcohol intake significantly. The authors discussed the results in terms of distraction and the effects of concurrently available reinforcers on alcohol self-administration.

  20. Acute lethal graft-versus-host disease stimulates cellular proliferation in the adult rat liver.

    PubMed

    Klein, R M; Clancy, J; Stuart, S

    1982-11-01

    The present investigation was designed to analyse the effects of acute lethal graft-versus-host disease (GVHD) in adult (DA x LEW)F1 rats on cellular proliferation within the liver. The influence of the host thymus on GVHD-induced proliferation was also assessed. From 1-28 days after initiation of GVHD [3H]thymidine ([3H]-TdR) was injected i.v. and rats were killed one hour later. Percentage labelled cells (LI) of periportal infiltrating cells (PIC), hepatocytes (H), and sinusoidal lining cells (SC) were counted. Mean values for control rats were 0.3 +/- 0.1% (H), 0.4 +/- 0.1% (SC) and 0.2 +/- 0.1% (PIC). GVHD rats demonstrated a significant increase in LI of PIC (days 1-21), SC (days 2-17) and H (days 2-17). Most labelled cells in PIC were large lymphocytes. Peak LI values were 7.0 +/- 1.0% PIC (day 17), 6.8 +/- 0.9% SC (day 17), and 5.2 +/- 0.9% H (day 7), with all cellular compartments returning to near normal LI values by day 28. Stimulation of cellular proliferation occurred in all three liver cell compartments in neonatally thymectomized (TXM) rats. The intensity of GVHD-induced cell proliferation was significantly decreased at day 7 in all compartments and PIC was dramatically decreased at day 21 in TXM-GVHD rats as compared to non-TXM-GVHD rats. It is hypothesized that the general stimulation of hepatocyte cell proliferation in GVHD is related to the secretion of lymphokines by primarily donor and secondarily host T cells in the periportal infiltrate. PMID:7172201

  1. Hypothyroidism increases prolactin secretion and decreases the intromission threshold for induction of pseudopregnancy in adult female rats.

    PubMed

    Tohei, A; Taya, K; Watanabe, G; Voogt, J L

    In order to understand the mechanism by which thyroid hormones alter prolactin (PRL) secretion, we investigated the role of tuberoinfundibular dopamine (TIDA) neurons and pituitary and hypothalamus vasoactive intestinal peptide (VIP) in thiouracil- (0. 03% in drinking water for 16 days) induced-hypothyroid adult female rats. The intromission threshold for induction of pseudopregnancy also was examined to evaluate the PRL response to coital stimulation in hypothyroid rats. Hypothyroidism in adult female rats did not affect TIDA neuronal activity as measured by tyrosine hydroxylase activity (DOPA accumulation 30 min after administration of m-hydroxybenzylhydrazine dihydrochloride, 100 mg/kg, i.p.) in the stalk-median eminence compared with that in euthyroid rats, whereas pituitary concentration of VIP was dramatically increased. Plasma concentration of PRL was higher at 1100 h of proestrus and estrus in hypothyroid rats as compared with that of euthyroid rats. The proportion of female rats exhibiting pseudopregnancy was higher in hypothyroid animals (100%) receiving seven intromissions than in euthyroid animals (43%). Administration of L-thyroxine in hypothyroid rats decreased the proportion of pseudopregnancy (40%) to the level of euthyroid animals. These results indicate that the increased level of pituitary VIP probably affects PRL secretion in a paracrine or autocrine manner and account for the hyperprolactinemia induced in hypothyroid female rats. No role for TIDA neurons in PRL elevation can be ascribed. A decrease in the intromission threshold for induction of pseudopregnancy might be due to increased levels of PRL in hypothyroid female rats.

  2. In vitro dermal absorption of pyrethroid pesticides in human and rat skin

    SciTech Connect

    Hughes, Michael F.; Edwards, Brenda C.

    2010-07-15

    Dermal exposure to pyrethroid pesticides can occur during manufacture and application. This study examined the in vitro dermal absorption of pyrethroids using rat and human skin. Dermatomed skin from adult male Long Evans rats or human cadavers was mounted in flow-through diffusion cells, and radiolabeled bifenthrin, deltamethrin or cis-permethrin was applied in acetone to the skin. Fractions of receptor fluid were collected every 4 h. At 24 h, the skins were washed with soap and water to remove unabsorbed chemical. The skin was then solubilized. Two additional experiments were performed after washing the skin; the first was tape-stripping the skin and the second was the collection of receptor fluid for an additional 24 h. Receptor fluid, skin washes, tape strips and skin were analyzed for radioactivity. For rat skin, the wash removed 53-71% of the dose and 26-43% remained in the skin. The cumulative percentage of the dose at 24 h in the receptor fluid ranged from 1 to 5%. For human skin, the wash removed 71-83% of the dose and 14-25% remained in the skin. The cumulative percentage of the dose at 24 h in the receptor fluid was 1-2%. Tape-stripping removed 50-56% and 79-95% of the dose in rat and human skin, respectively, after the wash. From 24-48 h, 1-3% and about 1% of the dose diffused into the receptor fluid of rat and human skin, respectively. The pyrethroids bifenthrin, deltamethrin and cis-permethrin penetrated rat and human skin following dermal application in vitro. However, a skin wash removed 50% or more of the dose from rat and human skin. Rat skin was more permeable to the pyrethroids than human skin. Of the dose in skin, 50% or more was removed by tape-stripping, suggesting that permeation of pyrethroids into viable tissue could be impeded. The percentage of the dose absorbed into the receptor fluid was considerably less than the dose in rat and human skin. Therefore, consideration of the skin type used and fractions analyzed are important when using

  3. Circadian rhythm of intraocular pressure in the adult rat.

    PubMed

    Lozano, Diana C; Hartwick, Andrew T E; Twa, Michael D

    2015-05-01

    Ocular hypertension is a risk factor for developing glaucoma, which consists of a group of optic neuropathies characterized by progressive degeneration of retinal ganglion cells and subsequent irreversible vision loss. Our understanding of how intraocular pressure damages the optic nerve is based on clinical measures of intraocular pressure that only gives a partial view of the dynamic pressure load inside the eye. Intraocular pressure varies over the course of the day and the oscillator regulating these daily changes has not yet been conclusively identified. The purpose of this study was to compare and contrast the circadian rhythms of intraocular pressure and body temperature in Brown Norway rats when these animals are housed in standard light-dark and continuous dim light (40-90 lux) conditions. The results from this study show that the temperature rhythm measured in continuous dim light drifted forward relative to external time, indicating that the rhythm was free running and being regulated by an internal biological clock. Also, the results show that there is a persistent, but dampened, circadian rhythm of intraocular pressure in continuous dim light and that the circadian rhythms of temperature and intraocular pressure are not synchronized by the same central oscillator. We conclude that once- or twice-daily clinical measures of intraocular pressure are insufficient to describe intraocular pressure dynamics. Similarly, our results indicate that, in experimental animal models of glaucoma, the common practice of housing animals in constant light does not necessarily eliminate the potential influence of intraocular pressure rhythms on the progression of nerve damage. Future studies should aim to determine whether an oscillator within the eye regulates the rhythm of intraocular pressure and to better characterize the impact of glaucoma on this rhythm.

  4. Developmental neurotoxicity of methanol exposure by inhalation in rats. Research report, June 1990-June 1994

    SciTech Connect

    Weiss, B.; Stern, S.; Soderholm, S.C.; Cox, C.; Sharma, A.

    1996-04-01

    The possibility of widespread methanol exposure via inhalation stemming from its adoption as an automotive fuel or fuel component arouses concern about the potential vulnerability of the fetal brain. This project was designed to help address such concerns by studying the behavior of neonate and adult Long-Evans hooded rats following perinatal exposure to methanol vapor at 4,500 ppm for six hours daily beginning on gestation day 6 with both dams and pups then being exposed through postnatal day (PND) 21. Blood methanol concentrations of the dams, measured immediately following a six-hour exposure, were approximately 500 to 800 micrograms/milliliter. Average blood methanol concentrations in the pups were about twice those of the dams. Neurotoxicity was assessed by behavioral tests used previously to reveal adverse effects following developmental exposures to ethanol, cocaine, heavy metals, and other agents. Exposure of neonates to methanol did not affect suckling latency and attachment on PND 5, or performance on the conditioned olfactory aversion test on PND 10. Exposure to methanol did alter performances in the motor activity tests. Methanol-exposed neonates were less active on PND 18, but more active on PND 25 than the equivalent control-group pups. Schedule-controlled running in adults displayed a complex interaction with treatment. Changes in performance over the course of training differed between males and females depending on exposure to methanol. The results of the complex stochastic reinforcement schedule revealed behavioral differences due to methanol exposure in adults that were relatively subtle in nature and appeared after a new pattern of contingencies was introduced.

  5. Differential Effects of Inhaled Toluene on Locomotor Activity in Adolescent and Adult Rats

    PubMed Central

    Batis, Jeffery C.; Hannigan, John H.; Bowen, Scott E.

    2010-01-01

    Inhalant abuse is a world-wide public health concern among adolescents. Most preclinical studies have assessed inhalant effects in adult animals leaving unclear how behavioral effects differ in younger animals. We exposed adolescent (postnatal day [PN] 28) and adult (PN90) male rats to toluene using 1 of 3 exposure patterns. These patterns modeled those reported in toluene abuse in teens and varied concentration, number and length of exposures, as well as the inter-exposure interval. Animals were exposed repeatedly over 12 days to toluene concentrations of 0, 8,000 or 16,000 parts per million (ppm). Locomotor activity was quantified during toluene exposures and for 30 min following completion of the final daily toluene exposure. For each exposure pattern, there were significant toluene concentration-related increases and decreases in locomotor activity compared to the 0-ppm “air” controls at both ages. These changes depended upon when activity was measured – during or following exposure. Compared to adults, adolescents displayed greater locomotor activity on the first day and generally greater increases in activity over days than adults during toluene exposure. Adults displayed greater locomotor activity than adolescents in the “recovery” period following exposure on the first and subsequent days. Age group differences were clearest following the pattern of paced, brief (5-min) repeated binge exposures. The results suggest that locomotor behavior in rats during and following inhalation of high concentrations of toluene depends on age and the pattern of exposure. The results are consistent with dose-dependent shifts in sensitivity and sensitization or tolerance to repeated toluene in the adolescent animals compared to the adult animals. Alternate interpretations are possible and our interpretation is limited by the range of very high concentrations of toluene used. The results imply that both pharmacological and psychosocial factors contribute to the teen

  6. Alterations in cytochrome P-450 levels in adult rats following neonatal exposure to xenobiotics

    SciTech Connect

    Zangar, R.C. Pacific Northwest Laboratories, Richland, WA ); Springer, D.L. ); Buhler, D.R. )

    1993-01-01

    Neonatal exposure to certain xenobiotics has been shown to alter hepatic metabolism in adult rats in a manner that indicates long-term changes in enzyme regulation. Previously, the authors have observed changes in adult testosterone metabolism and in cytochrome P-450 (P-450) mRNA levels in animals neonatally exposed to phenobarbital (PB) or diethylstilbestrol (DES). In order to test for other enzyme alterations, they used Western blot procedures for specific P-450s to analyze hepatic microsomes from adult rats (24 wk old) that had been exposed neonatally to DES, PB, 7,12-dimethylbenz[a]anthracene (DMBA), or pregnenolone 16[alpha]-carbonitrile (PCN). The most striking effects were observed in the DES-treated males: P-4502C6 and an immunologically similar protein were increased 60 and 90%, respectively, relative to control values, but P-4503A2 was decreased by 44%. No changes were observed in the DES-treated males in levels of P-4502E1, P-4502B, or the male-specific P-4502C13. Adult males neonatally treated with PB had 150% increase in levels of anti-P4502B-reactive protein without significant changes in the other enzymes. The DES- and DMBA-treated females had increased levels of the female-specific P-4502C12 of 38 and 48%, respectively, but no other observed alterations. The results confirm that neonatal exposure to DES or PB can cause alterations in adult hepatic cytochrome P-450 levels but show that these chemicals act on different enzymes. Neonatal DMBA resulted in changes in adult females similar to those produced by the synthetic estrogen DES, but did so at about two-thirds lower dose. 37 refs., 5 figs.

  7. Prenatal exposure to dexamethasone alters Leydig cell steroidogenic capacity in immature and adult rats.

    PubMed

    Page, K C; Sottas, C M; Hardy, M P

    2001-01-01

    This study examines the effects of prenatal exposure to dexamethasone (DEX) on postnatal testosterone production in male rats. Pregnant female rats were treated on gestation days 14-19 with DEX (100 microg/kg body weight per day; n = 9) or vehicle (n = 9). Results show that 35-day-old male offspring from DEX-treated pregnant females (n = 42) had decreased levels of serum testosterone (45.6% lower, P < .05) compared with control offspring (n = 43), although serum luteinizing hormone (LH) levels were not significantly altered. These findings suggest that a direct programming of developing gonadal cells occurs in response to high levels of maternal glucocorticoid. Indeed, testosterone production was significantly reduced in Leydig cells isolated from immature offspring of DEX-treated pregnant females compared with controls (48.3%, P < .001), and LH stimulation of these cells did not compensate for the lowered steroidogenic capacity. The hypothalamic-pituitary-adrenal axis was also affected, because significant reductions in both serum adrenocorticotropic hormone (ACTH; 26.2%, P < .001) and corticosterone (CORT; 32.3%, P < .001) were measured in DEX-exposed immature male offspring. In contrast, adult male offspring from DEX-treated dams had significantly higher levels of serum ACTH (39.2%, P <. 001) and CORT (37.8%, P < .001). These same animals had higher serum testosterone (31.6%, P < or = .05) and a significant reduction in serum LH (30.8%, P < .001). Moreover, Leydig cells isolated from these adult offspring exhibited an increased capacity for testosterone biosynthesis under basal (38.6%, P < .001) and LH-stimulated conditions (33.5%, P < .001). In summary, sustained changes in steroidogenic capacity were observed in male rats exposed to high levels of glucocorticoid during prenatal development. More specifically, DEX exposure in utero perturbed Leydig cell testosterone production in both pubertal and adult rats.

  8. Infrasound increases intracellular calcium concentration and induces apoptosis in hippocampi of adult rats.

    PubMed

    Liu, Zhaohui; Gong, Li; Li, Xiaofang; Ye, Lin; Wang, Bin; Liu, Jing; Qiu, Jianyong; Jiao, Huiduo; Zhang, Wendong; Chen, Jingzao; Wang, Jiuping

    2012-01-01

    In the present study, we determined the effect of infrasonic exposure on apoptosis and intracellular free Ca²⁺ ([Ca²⁺]i) levels in the hippocampus of adult rats. Adult rats were randomly divided into the control and infrasound exposure groups. For infrasound treatment, animals received infrasonic exposure at 90 (8 Hz) or 130 dB (8 Hz) for 2 h per day. Hippocampi were dissected, and isolated hippocampal neurons were cultured. The [Ca²⁺]i levels in hippocampal neurons from adult rat brains were determined by Fluo-3/AM staining with a confocal microscope system on days 1, 7, 14, 21 and 28 following infrasonic exposure. Apoptosis was evaluated by Annexin V-FITC and propidium iodide double staining. Positive cells were sorted and analyzed by flow cytometry. Elevated [Ca²⁺]i levels were observed on days 14 and 21 after rats received daily treatment with 90 or 130 dB sound pressure level (SPL) infrasonic exposure (p<0.01 vs. control). The highest levels of [Ca²⁺]i were detected in the 130 dB SPL infrasonic exposure group. Meanwhile, apoptosis in hippocampal neurons was found to increase on day 7 following 90 dB SPL infrasound exposure, and significantly increased on day 14. Upon 130 dB infrasound treatment, apoptosis was first observed on day 14, whereas the number of apoptotic cells gradually decreased thereafter. Additionally, a marked correlation between cell apoptosis and [Ca²⁺]i levels was found on day 14 and 21 following daily treatment with 90 and 130 dB SPL, respectively. These results demonstrate that a period of infrasonic exposure induced apoptosis and upregulated [Ca²⁺]i levels in hippocampal neurons, suggesting that infrasound may cause damage to the central nervous system (CNS) through the Ca²⁺‑mediated apoptotic pathway in hippocampal neurons. PMID:21946944

  9. Perinatal iron deficiency affects locomotor behavior and water maze performance in adult male and female rats.

    PubMed

    Bourque, Stephane L; Iqbal, Umar; Reynolds, James N; Adams, Michael A; Nakatsu, Kanji

    2008-05-01

    Iron deficiency during early growth and development adversely affects multiple facets of cognition and behavior in adult rats. The purpose of this study was to assess the nature of the learning and locomotor behavioral deficits observed in male and female rats in the absence of depressed brain iron levels at the time of testing. Adult female Wistar rats were fed either an iron-enriched diet (>225 mg/kg Fe) or an iron-restricted diet (3 mg/kg Fe) for 2 wk prior to and throughout gestation, and a nonpurified diet (270 mg/kg Fe) thereafter. Open-field (OF) and Morris water maze (MWM) testing began when the offspring reached early adulthood (12 wk). At birth, perinatal iron-deficient (PID) offspring had reduced (P < 0.001) hematocrits (-33%), liver iron stores (-83%), and brain iron concentrations (-38%) compared with controls. Although there were no differences in iron status in adults, the PID males and females exhibited reduced OF exploratory behavior, albeit only PID males had an aversion to the center of the apparatus (2.5 vs. 6.9% in controls, P < 0.001). Additionally, PID males required greater path lengths to reach the hidden platform in the MWM, had reduced spatial bias for the target quadrant, and had a tendency for greater thigmotactic behavior in the probe trials (16.5 vs. 13.0% in controls; P = 0.06). PID females had slower swim speeds in all testing phases (-6.2%; P < 0.001). These results suggest that PID has detrimental programming effects in both male and female rats, although the behaviors suggest different mechanisms may be involved in each sex.

  10. Efficacy of Retigabine on Acute Limbic Seizures in Adult Rats

    PubMed Central

    Friedman, LK; Slomko, AM; Wongvravit, JP; Naseer, Z; Hu, S; Wan, WY; Ali, SS

    2015-01-01

    Background and Purpose: The efficacy of retigabine (RGB), a positive allosteric modulator of K+ channels indicated for adjunct treatment of partial seizures, was studied in two adult models of kainic acid (KA)-induced status epilepticus to determine it’s toleratbility. Methods: Retigabine was administered systemiclly at high (5 mg/kg) and low (1–2 mg/kg) doses either 30 min prior to or 2 hr after KA-induced status epilepticus. High (1 µg/µL) and low (0.25 µg/µL) concentrations of RGB were also delivered by intrahippocampal microinjection in the presence of KA. Results: Dose-dependent effects of RGB were observed with both models. Lower doses increased seizure behavior latency and reduced the number of single spikes and synchronized burst events in the electroencephalogram (EEG). Higher doses worsened seizure behavior, produced severe ataxia, and increased spiking activity. Animals treated with RGB that were resistant to seizures did not exhibit significant injury or loss in GluR1 expression; however if stage 5–6 seizures were reached, typical hippocampal injury and depletion of GluR1 subunit protein in vulernable pyramidal fields occurred. Conclusions: RGB was neuroprotective only if seizures were significantly attenuated. GluR1 was simultaneously suppressed in the resistant granule cell layer in presence of RGB which may weaken excitatory transmission. Biphasic effects observed herein suggest that the human dosage must be carefully scrutinized to produce the optimal clinical response. PMID:26819936

  11. Histomorphometric evaluation of renal glomeruli exposed to sustained delivery of estrogen using adult ovariectomized rats.

    PubMed

    Hafez, Naiel A; Benghuzzi, Hamed; Tucci, Michelle

    2003-01-01

    Hormonal replacement therapy (HRT) has shown to be efficacious in treatment and preventing of heart disease, osteoporosis and reducing mortality in postmenopausal and ovariectomized females. Several attempts to utilize the native estrogen and its analogs such as Depo-Provera, conjugated estrogen and estrogen benzoate have shown different physiological responses. In addition, the route of administration and its mode of action is lacking in the literature. The specific objective of this study was to investigate the role of sustained delivery of estrogen on the functional and structural capacity of the kidney using adult female rats as a model. A total of 24 adult female rats were subdivided into four equal groups. Groups I and II were ovariectomized (OVX) by following standard laboratory surgical procedures. Each rat in groups II and III (intact) were implanted with tricalcium phosphate lysine (TCPL) drug delivery system loaded with 40 mg of estrogen. Rats in group IV were unimplanted and untreated to be served as a control group. At the end of 45 days post treatment the animals were sacrificed by using overdose of Halothane and assured by cervical dislocation. Vital and reproductive organs were retrieved, weighed and subjected to H&E staining procedure. The results of this investigation suggest: (i) TCPL delivery system released estrogen at a sustained level for 45 days without any untoward response, (ii) the wet weights of kidneys (normalized to body weight) were increased (p < 0.05) in intact rats treated with estrogen compared to control, (iii) sustained delivery of estrogen resulted in a maintenance of kidney weights compared to the control level, however, the lack of estrogen treatment resulted in a remarkable regression in the kidney weights of OVX rats, (iv) the ratio of renal arteries-diameter (normalized to arterial wall thickness) was significantly increased in intact rats treated with estrogen compared to the control and other experimental groups, (v

  12. Environmental enrichment alters glial antigen expression and neuroimmune function in the adult rat hippocampus.

    PubMed

    Williamson, Lauren L; Chao, Agnes; Bilbo, Staci D

    2012-03-01

    Neurogenesis is a well-characterized phenomenon within the dentate gyrus (DG) of the adult hippocampus. Environmental enrichment (EE) in rodents increases neurogenesis, enhances cognition, and promotes recovery from injury. However, little is known about the effects of EE on glia (astrocytes and microglia). Given their importance in neural repair, we predicted that EE would modulate glial phenotype and/or function within the hippocampus. Adult male rats were housed either 12 h/day in an enriched environment or in a standard home cage. Rats were injected with BrdU at 1 week, and after 7 weeks, half of the rats from each housing group were injected with lipopolysaccharide (LPS), and cytokine and chemokine expression was assessed within the periphery, hippocampus and cortex. Enriched rats had a markedly blunted pro-inflammatory response to LPS within the hippocampus. Specifically, expression of the chemokines Ccl2, Ccl3 and Cxcl2, several members of the tumor necrosis factor (TNF) family, and the pro-inflammatory cytokine IL-1β were all significantly decreased following LPS administration in EE rats compared to controls. EE did not impact the inflammatory response to LPS in the cortex. Moreover, EE significantly increased both astrocyte (GFAP+) and microglia (Iba1+) antigen expression within the DG, but not in the CA1, CA3, or cortex. Measures of neurogenesis were not impacted by EE (BrdU and DCX staining), although hippocampal BDNF mRNA was significantly increased by EE. This study demonstrates the importance of environmental factors on the function of the immune system specifically within the brain, which can have profound effects on neural function.

  13. A Microdialysis Study of the Medial Prefrontal Cortex of Adolescent and Adult Rats

    PubMed Central

    Staiti, Amanda M.; Morgane, Peter J.; Galler, Janina R.; Grivetti, Janice Y.; Bass, Donna C.; Mokler, David J.

    2011-01-01

    The medial prefrontal cortex (mPFC) of the rat has become a key focus of studies designed to elucidate the basis of behavior involving attention and decision making, i.e. executive functions. The adolescent mPFC is of particular interest given the role of the mPFC in impulsivity and attention, and disorders such as attentional deficit disorder. In the present study we have examined the basal extracellular concentrations of the neurotransmitters 5-hydroxytryptamine (5-HT), dopamine (DA) and norepinephrine (NE) in the ventral portion of the mPFC (vmPFC) in both adolescent (post-natal day 45–50) and adult, and male and female rats using in vivo microdialysis. We have also examined both the left and right vmPFCs given reports of laterality in function between the hemispheres. Basal extracellular concentrations of 5-HT differed significantly between male and female rats. Extracellular DA also differed significantly between male and female rats and between the left and the right vmPFC in adult males. No differences were seen in basal extracellular NE. There was a significant age difference between groups in the laterality of extracellular NE levels between right and left vmPFC. Infusion of 100 µM methamphetamine through the dialysis probe increased the extracellular concentration of all the monoamines although there were no differences between groups in methamphetamine stimulated release. The findings from this study demonstrate that there are differences in monoaminergic input to the mPFC of the rat based on age, gender and hemisphere. This work sets the neurochemical baseline for further investigations of the prefrontal cortex during development. PMID:21527264

  14. Acute and Chronic Effects of Dietary Lactose in Adult Rats Are not Explained by Residual Intestinal Lactase Activity.

    PubMed

    van de Heijning, Bert J M; Kegler, Diane; Schipper, Lidewij; Voogd, Eline; Oosting, Annemarie; van der Beek, Eline M

    2015-07-08

    Neonatal rats have a high intestinal lactase activity, which declines around weaning. Yet, the effects of lactose-containing products are often studied in adult animals. This report is on the residual, post-weaning lactase activity and on the short- and long-term effects of lactose exposure in adult rats. Acutely, the postprandial plasma response to increasing doses of lactose was studied, and chronically, the effects of a 30% lactose diet fed from postnatal (PN) Day 15 onwards were evaluated. Intestinal lactase activity, as assessed both in vivo and in vitro, was compared between both test methods and diet groups (lactose vs. control). A 50%-75% decreased digestive capability towards lactose was observed from weaning into adulthood. Instillation of lactose in adult rats showed disproportionally low increases in plasma glucose levels and did not elicit an insulin response. However, gavages comprising maltodextrin gave rise to significant plasma glucose and insulin responses, indicative of a bias of the adult GI tract to digest glucose polymers. Despite the residual intestinal lactase activity shown, a 30% lactose diet was poorly digested by adult rats: the lactose diet rendered the animals less heavy and virtually devoid of body fat, whereas their cecum tripled in size, suggesting an increased bacterial fermentation. The observed acute and chronic effects of lactose exposure in adult rats cannot be explained by the residual intestinal lactase activity assessed.

  15. Acute and Chronic Effects of Dietary Lactose in Adult Rats Are not Explained by Residual Intestinal Lactase Activity

    PubMed Central

    van de Heijning, Bert J. M.; Kegler, Diane; Schipper, Lidewij; Voogd, Eline; Oosting, Annemarie; van der Beek, Eline M.

    2015-01-01

    Neonatal rats have a high intestinal lactase activity, which declines around weaning. Yet, the effects of lactose-containing products are often studied in adult animals. This report is on the residual, post-weaning lactase activity and on the short- and long-term effects of lactose exposure in adult rats. Acutely, the postprandial plasma response to increasing doses of lactose was studied, and chronically, the effects of a 30% lactose diet fed from postnatal (PN) Day 15 onwards were evaluated. Intestinal lactase activity, as assessed both in vivo and in vitro, was compared between both test methods and diet groups (lactose vs. control). A 50%–75% decreased digestive capability towards lactose was observed from weaning into adulthood. Instillation of lactose in adult rats showed disproportionally low increases in plasma glucose levels and did not elicit an insulin response. However, gavages comprising maltodextrin gave rise to significant plasma glucose and insulin responses, indicative of a bias of the adult GI tract to digest glucose polymers. Despite the residual intestinal lactase activity shown, a 30% lactose diet was poorly digested by adult rats: the lactose diet rendered the animals less heavy and virtually devoid of body fat, whereas their cecum tripled in size, suggesting an increased bacterial fermentation. The observed acute and chronic effects of lactose exposure in adult rats cannot be explained by the residual intestinal lactase activity assessed. PMID:26184291

  16. Histological correlates of N40 auditory evoked potentials in adult rats after neonatal ventral hippocampal lesion: animal model of schizophrenia.

    PubMed

    Romero-Pimentel, A L; Vázquez-Roque, R A; Camacho-Abrego, I; Hoffman, K L; Linares, P; Flores, G; Manjarrez, E

    2014-11-01

    The neonatal ventral hippocampal lesion (NVHL) is an established neurodevelopmental rat model of schizophrenia. Rats with NVHL exhibit several behavioral, molecular and physiological abnormalities that are similar to those found in schizophrenics. Schizophrenia is a severe psychiatric illness characterized by profound disturbances of mental functions including neurophysiological deficits in brain information processing. These deficits can be assessed by auditory evoked potentials (AEPs), where schizophrenics exhibit abnormalities in amplitude, duration and latency of such AEPs. The aim of the present study was to compare the density of cells in the temporal cerebral cortex and the N40-AEP of adult NVHL rats versus adult sham rats. We found that rats with NVHL exhibit significant lower amplitude of the N40-AEP and a significant lower number of cells in bilateral regions of the temporal cerebral cortex compared to sham rats. Because the AEP recordings were obtained from anesthetized rats, we suggest that NVHL leads to inappropriate innervation in thalamic-cortical pathways in the adult rat, leading to altered function of cortical networks involved in processing of primary auditory information.

  17. 5,7-DHT-induced hippocampal 5-HT depletion attenuates behavioural deficits produced by 192 IgG-saporin lesions of septal cholinergic neurons in the rat.

    PubMed

    Lehmann, Olivia; Bertrand, Fabrice; Jeltsch, Hélène; Morer, Martine; Lazarus, Christine; Will, Bruno; Cassel, Jean-Christophe

    2002-06-01

    Adult Long-Evans male rats sustained injections of 5,7-dihydroxytryptamine into the fimbria-fornix (2.5 microg/side) and the cingular bundle (1.5 microg/side) and/or to intraseptal injections of 192 IgG-saporin (0.4 microg/side) in order to deprive the hippocampus of its serotonergic and cholinergic innervations, respectively. Sham-operated rats were used as controls. The rats were tested for locomotor activity (postoperative days 18, 42 and 65), spontaneous T-maze alternation (days 20-29), beam-walking sensorimotor (days 34-38), water maze (days 53-64) and radial maze (days 80-133) performances. The cholinergic lesions, which decreased the hippocampal concentration of ACh by about 65%, induced nocturnal hyperlocomotion, reduced T-maze alternation, impaired reference-memory in the water maze and working-memory in the radial maze, but had no effect on beam-walking scores and working-memory in the water maze. The serotonergic lesions, which decreased the serotonergic innervation of the hippocampus by about 55%, failed to induce any behavioural deficit. In the group of rats given combined lesions, all deficits produced by the cholinergic lesions were observed, but the nocturnal hyperlocomotion and the working-memory deficits in the radial maze were attenuated significantly. These results suggest that attenuation of the serotonergic tone in the hippocampus may compensate for some dysfunctions subsequent to the loss of cholinergic hippocampal inputs. This observation is in close concordance with data showing that a reduction of the serotonergic tone, by pharmacological activation of somatodendritic 5-HT(1A) receptors on raphe neurons, attenuates the cognitive disturbances produced by the intrahippocampal infusion of the antimuscarinic drug, scopolamine. This work has been presented previously [Serotonin Club/Brain Research Bulletin conference, Serotonin: From Molecule to the Clinic (satellite to the Society for Neuroscience Meeting, New Orleans, USA, November 2-3, 2000

  18. Ghrelin modulates testicular germ cells apoptosis and proliferation in adult normal rats

    SciTech Connect

    Kheradmand, Arash; Dezfoulian, Omid; Alirezaei, Masoud; Rasoulian, Bahram

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer Spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. Black-Right-Pointing-Pointer Numerous studies have documented the direct action of ghrelin in the modulation of apoptosis in different cell types. Black-Right-Pointing-Pointer Ghrelin may be considered as a modulator of spermatogenesis in normal adult rats. Black-Right-Pointing-Pointer Ghrelin may be potentially implicated for abnormal spermatogenesis in some testicular germ cell tumors. -- Abstract: Under normal condition in the most mammals, spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. The present study was designed to determine the effects of ghrelin treatment on in vivo quality and quantity expression of apoptosis and proliferation specific indices in rat testicular germ cells. Twenty eight adult normal rats were subdivided into equal control and treatment groups. Treatment group received 3 nmol of ghrelin as subcutaneous injection for 30 consecutive days or vehicle to the control animals. The rats from each group (n = 7) were killed on days 10 and 30 and their testes were taken for immunocytochemical evaluation and caspase-3 assay. Immunohistochemical analysis indicated that the accumulations of Bax and PCNA peptides are generally more prominent in spermatocytes and spermatogonia of both groups. Likewise, the mean percentage of immunoreactive spermatocytes against Bax increased (P < 0.01) in the ghrelin-treated group on day 10, while despite of 30% increment in the Bax level of spermatocytes in the treated rats on day 30, however, it was not statistically significant. During the experimental period, only a few spermatogonia represented Bax expression and the changes of Bax immunolabling cells were negligible upon ghrelin treatment. Likewise, there were immunostaining cells against Bcl-2 in each germ cell neither in the control nor in the treated animals. In fact

  19. Impacts of prenatal nanomaterial exposure on male adult Sprague-Dawley rat behavior and cognition.

    PubMed

    Engler-Chiurazzi, Elizabeth B; Stapleton, Phoebe A; Stalnaker, Jessica J; Ren, Xuefang; Hu, Heng; Nurkiewicz, Timothy R; McBride, Carroll R; Yi, Jinghai; Engels, Kevin; Simpkins, James W

    2016-01-01

    It is generally accepted that gestational xenobiotic exposures result in systemic consequences in the adult F1 generation. However, data on detailed behavioral and cognitive consequences remain limited. Using our whole-body nanoparticle inhalation facility, pregnant Sprague-Dawley rats (gestational day [GD] 7) were exposed 4 d/wk to either filtered air (control) or nano-titanium dioxide aerosols (nano-TiO2; count median aerodynamic diameter of 170.9 ± 6.4 nm, 10.4 ± 0.4 mg/m(3), 5 h/d) for 7.8 ± 0.5 d of the remaining gestational period. All rats received their final exposure on GD 20 prior to delivery. The calculated daily maternal deposition was 13.9 ± 0.5 µg. Subsequently, at 5 mo of age, behavior and cognitive functions of these pups were evaluated employing a standard battery of locomotion, learning, and anxiety tests. These assessments revealed significant working impairments, especially under maximal mnemonic challenge, and possible deficits in initial motivation in male F1 adults. Evidence indicates that maternal engineered nanomaterial exposure during gestation produces psychological deficits that persist into adulthood in male rats.

  20. Environmental enrichment for adult rats: effects on trait and state anxiety.

    PubMed

    Goes, Tiago Costa; Antunes, Fabrício Dias; Teixeira-Silva, Flavia

    2015-01-01

    Experimental evidence indicates that enriched environment (EE) induces neurobiological and behavioural alterations. EE in early life improves learning and memory and reduces trait and state anxiety. However, the effect of EE established in adulthood has rarely been investigated. Thus, the aim of this study was to evaluate the possibility of modifying the levels of trait and/or state anxiety of adult rats exposed to EE. Seventy adult Wistar male rats were first tested in the free-exploratory paradigm (FEP) and were categorized according to their levels of trait anxiety (high, medium and low). Subsequently, half of the animals from each category returned to their home cages (standard condition: SC) and the other half was transferred to an enriched environment (enriched condition: EC). After three weeks, all animals were again tested in FEP. Seven to 10 days later, fifty of the seventy animals were tested on the elevated plus-maze test (EPM). In FEP, EE reduced locomotor activity in the second exposition independently of the anxiety category and, it decreased the levels of trait anxiety of highly anxious rats. No effect of EE was observed on EPM. In conclusion, EE established in adulthood was able to reduce high trait anxiety, a major risk factor for anxiety disorders.

  1. Unilateral eye enucleation in adult rats causes neuronal loss in the contralateral superior colliculus

    PubMed Central

    SMITH, S. A.; BEDI, K. S.

    1997-01-01

    Several studies have reported the morphological changes induced by unilateral enucleation during early neonatal life on the developing visual system. This study has examined cellular changes in the superior colliculi by removal of a single eye in adult rats. Anaesthetised male hooded rats aged 90 d had their right eyes removed. Groups of nonenucleated control and enucleated rats were killed when aged either 150 or 390 d. The brains were removed and both the right and left superior colliculi dissected out. The volume of the stratum griseum superficiale (SGS) within these colliculi was estimated stereologically by light microscopy, as well as the numerical density and total number of neurons within this cell layer. The volume of the cell layer was reduced by about 40% on the side contralateral to the enucleated eye but not on the ipsilateral side at both survival periods examined. The numerical density of neurons within the SGS was unaffected by the enucleation so that the colliculi contralateral to the enucleated eye showed a substantial loss of neurons within this cell layer. This study demonstrates the importance of the retinal ganglion cell input, even in adult animals, for maintaining the viability of neurons in the SGS layer of the superior colliculus. PMID:9183672

  2. Maternal separation is associated with DNA methylation and behavioural changes in adult rats.

    PubMed

    Anier, Kaili; Malinovskaja, Kristina; Pruus, Katrin; Aonurm-Helm, Anu; Zharkovsky, Alexander; Kalda, Anti

    2014-03-01

    Early life stress is known to promote long-term neurobiological changes, which may underlie the increased risk of psychopathology. Maternal separation (MS) is used as an early life stressor that causes profound neurochemical and behavioural changes in the pups that persist into adulthood. However, the exact mechanism of how MS alters these behavioural changes is not yet understood. Epigenetic modifications, such as DNA methylation, are critical regulators of persistent gene expression changes and may be related to behavioural disorders. The aim of the present study was to investigate whether early life stress on rats could alter cocaine-induced behavioural sensitisation in adulthood via aberrant DNA methylation. We have three main findings: (1) MS increased DNA methyltransferases (DNMTs) expression in the nucleus accumbens (NAc) of infant and adult rats; (2) MS induced DNA hypomethylation on a global level in the NAc, and hypermethylation of the promoter regions of the protein phosphatase 1 catalytic subunit (PP1C) and adenosine A2Areceptor (A2AR) genes, which was associated with their transcriptional downregulation in the NAc; (3) MS-induced molecular changes paralleled an increased response to cocaine-induced locomotor activity and exploratory behaviour in adult rats. Thus, our results suggest that stressful experiences in early life may create a background, via aberrant DNA methylation, which promotes the development of cocaine-induced behavioural sensitisation in adulthood. PMID:23972903

  3. Impacts of prenatal nanomaterial exposure on male adult Sprague-Dawley rat behavior and cognition.

    PubMed

    Engler-Chiurazzi, Elizabeth B; Stapleton, Phoebe A; Stalnaker, Jessica J; Ren, Xuefang; Hu, Heng; Nurkiewicz, Timothy R; McBride, Carroll R; Yi, Jinghai; Engels, Kevin; Simpkins, James W

    2016-01-01

    It is generally accepted that gestational xenobiotic exposures result in systemic consequences in the adult F1 generation. However, data on detailed behavioral and cognitive consequences remain limited. Using our whole-body nanoparticle inhalation facility, pregnant Sprague-Dawley rats (gestational day [GD] 7) were exposed 4 d/wk to either filtered air (control) or nano-titanium dioxide aerosols (nano-TiO2; count median aerodynamic diameter of 170.9 ± 6.4 nm, 10.4 ± 0.4 mg/m(3), 5 h/d) for 7.8 ± 0.5 d of the remaining gestational period. All rats received their final exposure on GD 20 prior to delivery. The calculated daily maternal deposition was 13.9 ± 0.5 µg. Subsequently, at 5 mo of age, behavior and cognitive functions of these pups were evaluated employing a standard battery of locomotion, learning, and anxiety tests. These assessments revealed significant working impairments, especially under maximal mnemonic challenge, and possible deficits in initial motivation in male F1 adults. Evidence indicates that maternal engineered nanomaterial exposure during gestation produces psychological deficits that persist into adulthood in male rats. PMID:27092594

  4. Evidence of lactoferrin transportation into blood circulation from intestine via lymphatic pathway in adult rats.

    PubMed

    Takeuchi, Takashi; Kitagawa, Hiroshi; Harada, Etsumori

    2004-05-01

    Using adult rats, the characteristic transporting system for lactoferrin (LF) from intestinal lumen into the blood circulation was investigated. The rats were randomly divided into two groups, a non-collected thoracic lymph (NC) group and a collected thoracic lymph (LC) group. Peripheral blood and thoracic lymph were collected from a jugular vein and a thoracic lymph duct, respectively, under anaesthesia. Bovine LF (bLF) was infused into the duodenal lumen by needle over a 1-min period at a dose of 1 g kg(-1). The transported bLF in the plasma and lymph was assayed quantitatively by double-antibody enzyme-linked immunosorbent assay (ELISA). Morphological investigation was also carried out in the intestine, lymph node, and liver. Following intraduodenal administration of bLF, the transported bLF in the NC group was detected in the plasma, and reached a peak value at 2 h. Furthermore, the bLF concentration in the thoracic duct lymph fluid in the LC group increased significantly, and peaked 2 h after the administration. In addition, bLF was not detected in the plasma of the LC group. Immunohistochemical analysis clearly showed anti-bLF positive particles in the epithelial cells of the apical villi. The striated border and baso-lateral membrane were also bLF positive. These results suggest that intraduodenally infused bLF is transported into the blood circulation via the lymphatic pathway, not via portal circulation in adult rats.

  5. Gender differences in the effect of adult amphetamine on cognitive functions of rats prenatally exposed to methamphetamine.

    PubMed

    Macúchová, E; Nohejlová, K; Slamberová, R

    2014-08-15

    Psychostimulants have been shown to affect brain regions involved in the process of learning and memory consolidation. It has been shown that females are more sensitive to the effects of drugs than males. The aim of our study was to investigate how prenatal methamphetamine (MA) exposure and application of amphetamine (AMP) in adulthood would affect spatial learning of adult female and male rats. Mothers of the tested offspring were exposed to injections of MA (5mg/kg) or saline (SA) throughout the entire gestation period. Cognitive functions of adult rats were evaluated in the Morris Water Maze (MWM) tests. Adult offspring were injected daily with AMP (5mg/kg) or SA through the period of MWM testing. Our data from the MWM tests demonstrates the following. Prenatal MA exposure did not change the learning ability of adult male and female rats. However, AMP administration to adult animals affected cognitive function in terms of exacerbation of spatial learning (increasing the latency to reach the hidden platform, the distance traveled and the search error) only in female subjects. There were sex differences in the speed of swimming. Prenatal MA exposure and adult AMP treatment increased the speed of swimming in female groups greater than in males. Overall, the male subjects showed a better learning ability than females. Thus, our results indicate that the adult AMP treatment affects the cognitive function and behavior of rats in a sex-specific manner, regardless of prenatal exposure.

  6. Integrated phrenic responses to carotid afferent stimulation in adult rats following perinatal hyperoxia.

    PubMed Central

    Ling, L; Olson, E B; Vidruk, E H; Mitchell, G S

    1997-01-01

    1. Hypoxic ventilatory responses are greatly attenuated in adult rats exposed to moderate hyperoxia (60% O2) during the first month of life (perinatal treated rats). The present study was designed to test the hypothesis that perinatal hyperoxia impairs central integration of carotid chemoreceptor afferent inputs, thereby diminishing the hypoxic ventilatory response. 2. Time-dependent phrenic nerve responses to electrical stimulation of the carotid sinus nerve (CSN) and steady-state relationships between CSN stimulation frequency and phrenic nerve output were compared in control and perinatal treated rats. The rats were urethane anaesthetized, vagotomized, paralysed and artificially ventilated. End-tidal CO2 was monitored and maintained at isocapnic levels; arterial blood gases were determined. 3. Two stimulation protocols were used: (1) three 2 min episodes of CSN stimulation (20 Hz, 0.2 ms duration, 3 x threshold), separated by 5 min intervals; and (2) nine 45 s episodes of CSN stimulation with stimulus frequencies ranging from 0.5 to 20 Hz (0.2 ms duration, 3 x threshold), separated by 4 min intervals. 4. The mean threshold currents to elicit phrenic responses were similar between groups. Burst frequency (f, burst min-1), peak amplitude of integrated phrenic activity (integral of Phr), and minute phrenic activity (integral of Phr x f) during and after CSN stimulation were not distinguishable between groups in either protocol at any time or at any stimulus intensity (P > 0.05). 5. Perinatal hyperoxia does not alter temporal or steady-state phrenic responses to CSN stimulation, suggesting that the central integration of carotid chemoreceptor afferent inputs is not impaired in perinatal treated rats. It is speculated that carotid chemoreceptors per se are impaired in perinatal treated rats. PMID:9161991

  7. Impaired contextual fear extinction and hippocampal synaptic plasticity in adult rats induced by prenatal morphine exposure.

    PubMed

    Tan, Ji-Wei; Duan, Ting-Ting; Zhou, Qi-Xin; Ding, Ze-Yang; Jing, Liang; Cao, Jun; Wang, Li-Ping; Mao, Rong-Rong; Xu, Lin

    2015-07-01

    Prenatal opiate exposure causes a series of neurobehavioral disturbances by affecting brain development. However, the question of whether prenatal opiate exposure increases vulnerability to memory-related neuropsychiatric disorders in adult offspring remains largely unknown. Here, we found that rats prenatally exposed to morphine (PM) showed impaired acquisition but enhanced maintenance of contextual fear memory compared with control animals that were prenatally exposed to saline (PS). The impairment of acquisition was rescued by increasing the intensity of footshocks (1.2 mA rather than 0.8 mA). Meanwhile, we also found that PM rats exhibited impaired extinction of contextual fear, which is associated with enhanced maintenance of fear memory. The impaired extinction lasted for 1 week following extinction training. Furthermore, PM rats exhibited reduced anxiety-like behavior in the elevated plus-maze and light/dark box test without differences in locomotor activity. These alterations in PM rats were mirrored by abnormalities in synaptic plasticity in the Schaffer collateral-CA1 synapses of the hippocampus in vivo. PS rats showed blocked long-term potentiation and enabled long-term depression in CA1 synapses following contextual fear conditioning, while prenatal morphine exposure restricted synaptic plasticity in CA1 synapses. The smaller long-term potentiation in PM rats was not further blocked by contextual fear conditioning, and the long-term depression enabled by contextual fear conditioning was abolished. Taken together, our results provide the first evidence suggesting that prenatal morphine exposure may increase vulnerability to fear memory-related neuropsychiatric disorders in adulthood.

  8. Nuclear transfer of adult and genetically modified fetal cells of the rat.

    PubMed

    Hayes, E; Galea, S; Verkuylen, A; Pera, M; Morrison, J; Lacham-Kaplan, O; Trounson, A

    2001-04-27

    The present study examines the handling, activation, and micromanipulation of rat eggs in an attempt to produce live young using nuclear transfer (NT) of adult and genetically modified rat fetal cells. Mature rat eggs cultured in calcium-free medium showed reduced rates (24%) of chromosomal dispersion ("spontaneous activation" characteristic of this species) compared with eggs cultured in calcium-containing medium (47%), but failed to survive micromanipulation procedures. High rates of parthenogenetic cleavage were obtained with chemical activation using ethanol/cycloheximide (65%) compared with other standard chemical activation methods (4-28%). This type of activation was also effective in reestablishing cleavage capability (19-71%), in a time-dependent manner, of spontaneously activated eggs arrested at a second prophase-like state. At most, two of four tested micromanipulation procedures were effective in producing NT embryos capable of morula or blastocyst development (14-16%) in vivo following transfer to mouse oviducts. NT blastocysts produced from cumulus cells and transfected rat fetal fibroblasts appeared morphologically and karyotypically normal (2n = 42). Nocodazole-assisted metaphase enucleation and piezoelectric-assisted donor cell injection produced significant and equivocal effects on survival and cleavage rates of reconstructed embryos but failed to significantly improve in vivo morula/blastocyst development rates (16-28%) compared with unassisted micromanipulation (16%). Live births have not yet been obtained from early cleavage stage embryos (n = 269) transferred to pseudopregnant recipient rat oviducts. Improvements in reconstituted NT embryo culture and transfer are required for these methods to be an effective means of transgenic rat production.

  9. Homeostatic regulation of adult hippocampal neurogenesis in aging rats: long-term effects of early exercise

    PubMed Central

    Merkley, Christina M.; Jian, Charles; Mosa, Adam; Tan, Yao-Fang; Wojtowicz, J. Martin

    2014-01-01

    Adult neurogenesis is highly responsive to environmental and physiological factors. The majority of studies to date have examined short-term consequences of enhancing or blocking neurogenesis but long-term changes remain less well understood. Current evidence for age-related declines in neurogenesis warrant further investigation into these long-term changes. In this report we address the hypothesis that early life experience, such as a period of voluntary running in juvenile rats, can alter properties of adult neurogenesis for the remainder of the animal's life. The results indicate that the number of proliferating and differentiating neuronal precursors is not altered in runners beyond the initial weeks post-running, suggesting homeostatic regulation of these processes. However, the rate of neuronal maturation and survival during a 4 week period after cell division was enhanced up to 11 months of age (the end of the study period). This study is the first to show that a transient period of physical activity at a young age promotes changes in neurogenesis that persist over the long-term, which is important for our understanding of the modulation of neurogenesis by exercise with age. Functional integration of adult-born neurons within the hippocampus that resist homeostatic regulation with aging, rather than the absolute number of adult-born neurons, may be an essential feature of adult neurogenesis that promotes the maintenance of neural plasticity in old age. PMID:25071426

  10. Anti-Nogo-A Immunotherapy Does Not Alter Hippocampal Neurogenesis after Stroke in Adult Rats

    PubMed Central

    Shepherd, Daniel J.; Tsai, Shih-Yen; O'Brien, Timothy E.; Farrer, Robert G.; Kartje, Gwendolyn L.

    2016-01-01

    Ischemic stroke is a leading cause of adult disability, including cognitive impairment. Our laboratory has previously shown that treatment with function-blocking antibodies against the neurite growth inhibitory protein Nogo-A promotes functional recovery after stroke in adult and aged rats, including enhancing spatial memory performance, for which the hippocampus is critically important. Since spatial memory has been linked to hippocampal neurogenesis, we investigated whether anti-Nogo-A treatment increases hippocampal neurogenesis after stroke. Adult rats were subject to permanent middle cerebral artery occlusion followed 1 week later by 2 weeks of antibody treatment. Cellular proliferation in the dentate gyrus was quantified at the end of treatment, and the number of newborn neurons was determined at 8 weeks post-stroke. Treatment with both anti-Nogo-A and control antibodies stimulated the accumulation of new microglia/macrophages in the dentate granule cell layer, but neither treatment increased cellular proliferation or the number of newborn neurons above stroke-only levels. These results suggest that anti-Nogo-A immunotherapy does not increase post-stroke hippocampal neurogenesis. PMID:27803646

  11. Sodium metabisulfite-induced changes on testes, spermatogenesis and epididymal morphometric values in adult rats

    PubMed Central

    Shekarforoush, Shahnaz; Ebrahimi, Zahra; Hoseini, Maryam

    2015-01-01

    Background: Sulphites are widely used as a preservative and antioxidant additives in the food and pharmaceutical industries. Many types of biological and toxicological effects of sulphites in multiple organs of mammals have been shown in previous studies. Objective: The aim of this study was to investigate the effects of sodium metabisulfite (SMB) on testicular function and morphometric values of epididymis in adult male Wistar rats. Materials and Methods: A total of 32 rats were randomly divided into four groups. The experimental groups received SMB at doses of 10 mg/kg (S10), 100mg/kg (S100), and 260 mg/kg (S260) while an equal volume of normal saline was administered to the control group via gavage. The rats were anaesthetized after 28 days and the left testis with the head of epididimis was excised following abdominal incision for histological observation using hematoxylin and eosin staining. Serum samples were collected for assay of testosterone level. The initial epididymis was analyzed for motility, morphology, and the number of sperms. Result: The results of this study showed that normal morphology, count, and motility of sperms and testosterone level were decreased in the SMB treated groups. In comparison with the control group, SMB resulted in a lower total number of spermatogonia, primary spermatocyte, spermatids, and Leydig cells. Conclusion: It is suggested that SMB decreases the sperm production and has the potential to affect the fertility adversely in male rats. PMID:27141536

  12. Lifespan Changes in the Countermanding Performance of Young and Middle Aged Adult Rats

    PubMed Central

    Beuk, Jonathan; Beninger, Richard J.; Paré, Martin

    2016-01-01

    Inhibitory control can be investigated with the countermanding task, which requires subjects to make a response to a go signal and cancel that response when a stop signal is presented occasionally. Adult humans performing the countermanding task typically exhibit impaired response time (RT), stop signal response time (SSRT) and response accuracy as they get older, but little change in post-error slowing. Rodent models of the countermanding paradigm have been developed recently, yet none have directly examined age-related changes in performance throughout the lifespan. Male Wistar rats (N = 16) were trained to respond to a visual stimulus (go signal) by pressing a lever directly below an illuminated light for food reward, but to countermand the lever press subsequent to a tone (stop signal) that was presented occasionally (25% of trials) at a variable delay. Subjects were tested in 1 h sessions at approximately 7 and 12 months of age with intermittent training in between. Rats demonstrated longer go trial RT, a higher proportion of go trial errors and performed less total trials at 12, compared to 7 months of age. Consistent SSRT and post-error slowing were observed for rats at both ages. These results suggest that the countermanding performance of rats does vary throughout the lifespan, in a manner similar to humans, suggesting that rodents may provide a suitable model for behavioral impairment related to normal aging. These findings also highlight the importance of indicating the age at which rodents are tested in countermanding investigations. PMID:27555818

  13. Lifespan Changes in the Countermanding Performance of Young and Middle Aged Adult Rats.

    PubMed

    Beuk, Jonathan; Beninger, Richard J; Paré, Martin

    2016-01-01

    Inhibitory control can be investigated with the countermanding task, which requires subjects to make a response to a go signal and cancel that response when a stop signal is presented occasionally. Adult humans performing the countermanding task typically exhibit impaired response time (RT), stop signal response time (SSRT) and response accuracy as they get older, but little change in post-error slowing. Rodent models of the countermanding paradigm have been developed recently, yet none have directly examined age-related changes in performance throughout the lifespan. Male Wistar rats (N = 16) were trained to respond to a visual stimulus (go signal) by pressing a lever directly below an illuminated light for food reward, but to countermand the lever press subsequent to a tone (stop signal) that was presented occasionally (25% of trials) at a variable delay. Subjects were tested in 1 h sessions at approximately 7 and 12 months of age with intermittent training in between. Rats demonstrated longer go trial RT, a higher proportion of go trial errors and performed less total trials at 12, compared to 7 months of age. Consistent SSRT and post-error slowing were observed for rats at both ages. These results suggest that the countermanding performance of rats does vary throughout the lifespan, in a manner similar to humans, suggesting that rodents may provide a suitable model for behavioral impairment related to normal aging. These findings also highlight the importance of indicating the age at which rodents are tested in countermanding investigations. PMID:27555818

  14. A comprehensive study of long-term skeletal changes after spinal cord injury in adult rats.

    PubMed

    Lin, Tiao; Tong, Wei; Chandra, Abhishek; Hsu, Shao-Yun; Jia, Haoruo; Zhu, Ji; Tseng, Wei-Ju; Levine, Michael A; Zhang, Yejia; Yan, Shi-Gui; Liu, X Sherry; Sun, Dongming; Young, Wise; Qin, Ling

    2015-01-01

    Spinal cord injury (SCI)-induced bone loss represents the most severe osteoporosis with no effective treatment. Past animal studies have focused primarily on long bones at the acute stage using adolescent rodents. To mimic chronic SCI in human patients, we performed a comprehensive analysis of long-term structural and mechanical changes in axial and appendicular bones in adult rats after SCI. In this experiment, 4-month-old Fischer 344 male rats received a clinically relevant T13 contusion injury. Sixteen weeks later, sublesional femurs, tibiae, and L4 vertebrae, supralesional humeri, and blood were collected from these rats and additional non-surgery rats for micro-computed tomography (µCT), micro-finite element, histology, and serum biochemical analyses. At trabecular sites, extreme losses of bone structure and mechanical competence were detected in the metaphysis of sublesional long bones after SCI, while the subchondral part of the same bones showed much milder damage. Marked reductions in bone mass and strength were also observed in sublesional L4 vertebrae but not in supralesional humeri. At cortical sites, SCI induced structural and strength damage in both sub- and supralesional long bones. These changes were accompanied by diminished osteoblast number and activity and increased osteoclast number and activity. Taken together, our study revealed site-specific effects of SCI on bone and demonstrated sustained inhibition of bone formation and elevation of bone resorption at the chronic stage of SCI. PMID:26528401

  15. Tianeptine facilitates spreading depression in well-nourished and early-malnourished adult rats.

    PubMed

    Amancio-Dos-Santos, Angela; Maia, Luciana Maria Silva de Seixas; Germano, Paula Catirina Pereira da Silva; Negrão, Yleana Danielle Dos Santos; Guedes, Rubem Carlos Araújo

    2013-04-15

    Nutritional status during development can modify the brain's electrophysiological properties and its response to drugs that reduce the serotonin availability in the synaptic cleft. Here we used cortical spreading depression (CSD) in the rat as a neurophysiological parameter to investigate the interaction between nutritional status and treatment with tianeptine, a serotonin uptake enhancer. From postnatal day 2 to 24, well-nourished and early-malnourished rat pups were s.c. injected with tianeptine (5 or 10mg/kg; 10 ml/kg) or equivalent volume of saline solution (control group). When the animals were 25-30 days old, CSD was recorded on the brain cortical surface. In the well-nourished rats, but not in the malnourished group, systemic tianeptine dose-dependently increased the CSD propagation velocity, with 10mg/kg producing a significant (P<0.05) effect. An experiment in adult rats showed that cortical topical application of tianeptine solutions (5mg/ml, 10mg/ml, and 20mg/ml) increased the CSD propagation in both the well-nourished and early-malnourished conditions. In well-nourished animals, 0.5mg/ml topical tianeptine did not affect CSD propagation, and 2mg/ml produced a small, but significant CSD acceleration. Our results indicate a facilitating action of tianeptine on CSD propagation, probably via tianeptine's pharmacological action on the serotonin system. These findings support previous data suggesting an antagonistic role of the serotoninergic system on CSD.

  16. A comprehensive study of long-term skeletal changes after spinal cord injury in adult rats

    PubMed Central

    Lin, Tiao; Tong, Wei; Chandra, Abhishek; Hsu, Shao-Yun; Jia, Haoruo; Zhu, Ji; Tseng, Wei-Ju; Levine, Michael A; Zhang, Yejia; Yan, Shi-Gui; Liu, X Sherry; Sun, Dongming; Young, Wise; Qin, Ling

    2015-01-01

    Spinal cord injury (SCI)-induced bone loss represents the most severe osteoporosis with no effective treatment. Past animal studies have focused primarily on long bones at the acute stage using adolescent rodents. To mimic chronic SCI in human patients, we performed a comprehensive analysis of long-term structural and mechanical changes in axial and appendicular bones in adult rats after SCI. In this experiment, 4-month-old Fischer 344 male rats received a clinically relevant T13 contusion injury. Sixteen weeks later, sublesional femurs, tibiae, and L4 vertebrae, supralesional humeri, and blood were collected from these rats and additional non-surgery rats for micro-computed tomography (µCT), micro-finite element, histology, and serum biochemical analyses. At trabecular sites, extreme losses of bone structure and mechanical competence were detected in the metaphysis of sublesional long bones after SCI, while the subchondral part of the same bones showed much milder damage. Marked reductions in bone mass and strength were also observed in sublesional L4 vertebrae but not in supralesional humeri. At cortical sites, SCI induced structural and strength damage in both sub- and supralesional long bones. These changes were accompanied by diminished osteoblast number and activity and increased osteoclast number and activity. Taken together, our study revealed site-specific effects of SCI on bone and demonstrated sustained inhibition of bone formation and elevation of bone resorption at the chronic stage of SCI. PMID:26528401

  17. Tianeptine facilitates spreading depression in well-nourished and early-malnourished adult rats.

    PubMed

    Amancio-Dos-Santos, Angela; Maia, Luciana Maria Silva de Seixas; Germano, Paula Catirina Pereira da Silva; Negrão, Yleana Danielle Dos Santos; Guedes, Rubem Carlos Araújo

    2013-04-15

    Nutritional status during development can modify the brain's electrophysiological properties and its response to drugs that reduce the serotonin availability in the synaptic cleft. Here we used cortical spreading depression (CSD) in the rat as a neurophysiological parameter to investigate the interaction between nutritional status and treatment with tianeptine, a serotonin uptake enhancer. From postnatal day 2 to 24, well-nourished and early-malnourished rat pups were s.c. injected with tianeptine (5 or 10mg/kg; 10 ml/kg) or equivalent volume of saline solution (control group). When the animals were 25-30 days old, CSD was recorded on the brain cortical surface. In the well-nourished rats, but not in the malnourished group, systemic tianeptine dose-dependently increased the CSD propagation velocity, with 10mg/kg producing a significant (P<0.05) effect. An experiment in adult rats showed that cortical topical application of tianeptine solutions (5mg/ml, 10mg/ml, and 20mg/ml) increased the CSD propagation in both the well-nourished and early-malnourished conditions. In well-nourished animals, 0.5mg/ml topical tianeptine did not affect CSD propagation, and 2mg/ml produced a small, but significant CSD acceleration. Our results indicate a facilitating action of tianeptine on CSD propagation, probably via tianeptine's pharmacological action on the serotonin system. These findings support previous data suggesting an antagonistic role of the serotoninergic system on CSD. PMID:23499681

  18. Thymoquinone supplementation ameliorates lead-induced testis function impairment in adult rats.

    PubMed

    Mabrouk, Aymen; Ben Cheikh, Hassen

    2016-06-01

    This study was realized to investigate the possible beneficial effect of thymoquinone (TQ), the major active component of volatile oil of Nigella sativa seeds, against lead (Pb)-induced inhibition of rat testicular functions. Adult rats were randomized into four groups: a control group receiving no treatment; a Pb group exposed to 2000 parts per million (ppm) of Pb acetate in drinking water; a Pb-TQ group co-treated with Pb (as in Pb group) plus TQ (5 mg/kg body weight (b.w.)/day, per orally (p.o.)); and a TQ group receiving TQ (5 mg/kg b.w./day, p.o.). All treatments were for 5 weeks. No significant differences were observed for the body weight gain or for relative testes weight among the four groups of animals. Testicular Pb content significantly increased in metal-intoxicated rats compared with that in control rats. TQ supplementation had no effect on this testicular Pb accumulation. Interestingly, when coadministrated with Pb, TQ significantly improved the low plasma testosterone level and the decreased epididymal sperm count caused by Pb. In conclusion, the results suggest, for the first time, that TQ protects against Pb-induced impairment of testicular steroidogenic and spermatogenic functions. This study will open new perspectives for the clinical use of TQ in Pb intoxication.

  19. The longitudinal study of rat hippocampus influenced by stress: early adverse experience enhances hippocampal vulnerability and working memory deficit in adult rats.

    PubMed

    Jin, Fengkui; Li, Lei; Shi, Mei; Li, Zhenzi; Zhou, Jinghua; Chen, Li

    2013-06-01

    Epidemiologic studies indicate that early adverse experience is related to learning disabilities in adults, but the neurobiological mechanisms have not yet been identified. We used longitudinal animal experiments to test the hypothesis that early life stress enhances hippocampal vulnerability and working memory deficit in adult rats. The expression of Synaptophysin (SYN) and apoptosis (Apo) in hippocampal CA3 and dentate gyrus (DG) regions were examined to evaluate the effects of environmental factors on the hippocampus. The working memory errors via radial 8-arm maze were studied to evaluate the long-term effect of early stress on rats' spatial learning ability. Our results indicated that chronic restraint stress in early life and forced cold water swimming stress in adulthood reduced SYN expression and increased Apo levels in rat hippocampus, but the hippocampal damage tended to recover when rats returned to a non-stress environment. In addition, when the rats were exposed to forced cold water swimming stress during adulthood, SYN expression (CA3 and DG regions) and Apo levels (CA3 region) in rat hippocampus showed statistical difference between early restraint stress group and non-early restraint stress group (rats exposed to stress in adulthood only). One month after the two groups of rats returned to non-stress environment, this difference of SYN expression (CA3 and DG regions) and working memory deficit between the two groups was still statistically significant. Our study findings suggested that early adverse experience enhances hippocampal vulnerability and working memory deficit in adult rats, and reduces structural plasticity of hippocampus.

  20. Tissue response of defined collagen-elastin scaffolds in young and adult rats with special attention to calcification.

    PubMed

    Daamen, W F; Nillesen, S T M; Hafmans, T; Veerkamp, J H; van Luyn, M J A; van Kuppevelt, T H

    2005-01-01

    Collagen-elastin scaffolds may be valuable biomaterials for tissue engineering because they combine tensile strength with elasticity. In this study, the tissue response to and the calcification of these scaffolds were evaluated. In particular, the hypothesis was tested that calcification, a common phenomenon in biomaterials, may be due to microfibrils within the elastic fibre, and that these microfibrils might generate a tissue response. Four scaffolds were subcutaneously implanted, viz. collagen, collagen + pure elastin, collagen+microfibril-containing, and collagen + pulverised elastic ligament (the source for elastin). Explants were evaluated at day 3, 7 and 21. In young Sprague Dawley rats, collagen + ligament calcified substantially, whereas collagen + elastin (with and without microfibrils) calcified less, and collagen did not. Calcification started at elastic fibres. In both Sprague Dawley and Wistar adult rats, however, none of the scaffolds calcified. Mononuclear cell infiltration was prominent in young and adult Sprague Dawley rats. In adult Wistar rats, this infiltration was associated with the presence of microfibrils. Degradation of scaffolds and new matrix formation were related with cellular influx and degree of vascularisation. In conclusion, absence of microfibrils from the elastic fibre does not prevent calcification in young Sprague Dawley rats, but does reduce the tissue response in adult Wistar rats. Cellular response and calcification differs with age and strain and therefore the choice of animal model is of key importance in biomaterial evaluation.

  1. Moderate prenatal alcohol exposure and quantification of social behavior in adult rats.

    PubMed

    Hamilton, Derek A; Magcalas, Christy M; Barto, Daniel; Bird, Clark W; Rodriguez, Carlos I; Fink, Brandi C; Pellis, Sergio M; Davies, Suzy; Savage, Daniel D

    2014-01-01

    Alterations in social behavior are among the major negative consequences observed in children with Fetal Alcohol Spectrum Disorders (FASDs). Several independent laboratories have demonstrated robust alterations in the social behavior of rodents exposed to alcohol during brain development across a wide range of exposure durations, timing, doses, and ages at the time of behavioral quantification. Prior work from this laboratory has identified reliable alterations in specific forms of social interaction following moderate prenatal alcohol exposure (PAE) in the rat that persist well into adulthood, including increased wrestling and decreased investigation. These behavioral alterations have been useful in identifying neural circuits altered by moderate PAE(1), and may hold importance for progressing toward a more complete understanding of the neural bases of PAE-related alterations in social behavior. This paper describes procedures for performing moderate PAE in which rat dams voluntarily consume ethanol or saccharin (control) throughout gestation, and measurement of social behaviors in adult offspring. PMID:25549080

  2. Analysis of proteome changes in doxorubicin-treated adult rat cardiomyocyte

    PubMed Central

    Kumar, Suresh N.; Konorev, Eugene A.; Aggarwal, Deepika; Kalyanaraman, Balaraman

    2011-01-01

    Doxorubicin-induced cardiomyopathy in cancer patients is well established. The proposed mechanism of cardiac damage includes generation of reactive oxygen species, mitochondrial dysfunction and cardiomyocyte apoptosis. Exposure of adult rat cardiomyocytes to low levels of DOX for 48 h induced apoptosis. Analysis of protein expression showed a differential regulation of several key proteins including the voltage dependent anion selective channel protein 2 and methylmalonate semialdehyde dehydrogenase. In comparison, proteomic evaluation of DOX-treated rat heart showed a slightly different set of protein changes that suggests nuclear accumulation of DOX. Using a new solubilization technique, changes in low abundant protein profiles were monitored. Altered protein expression, modification and function related to oxidative stress response may play an important role in DOX cardiotoxicity. PMID:21338723

  3. The 14-day repeated dose liver micronucleus test with methapyrilene hydrochloride using young adult rats.

    PubMed

    Inoue, Kenji; Ochi, Akimu; Koda, Akira; Wako, Yumi; Kawasako, Kazufumi; Doi, Takaaki

    2015-03-01

    The repeated dose liver micronucleus (RDLMN) assay using young adult rats has the potential to detect genotoxic hepatocarcinogens that can be integrated into a general toxicity study. The assay methods were thoroughly validated by 19 Japanese facilities. Methapyrilene hydrochloride (MP), known to be a non-genotoxic hepatocarcinogen, was examined in the present study. MP was dosed orally at 10, 30 and 100mg/kg/day to 6-week-old male Crl:CD (SD) rats daily for 14 days. Treatment with MP resulted in an increase in micronucleated hepatocytes (MNHEPs) with a dosage of only 100mg/kg/day. At this dose level, cytotoxicity followed by regenerative cell growth was noted in the liver. These findings suggest that MP may induce clastogenic effects indirectly on the liver or hepatotoxicity of MP followed by regeneration may cause increase in spontaneous incidence of MNHEPs.

  4. Functional evidence of α1D-adrenoceptors in the vasculature of young and adult spontaneously hypertensive rats

    PubMed Central

    Villalobos-Molina, Rafael; López-Guerrero, J Javier; Ibarra, Maximiliano

    1999-01-01

    The role of α1D-adrenoceptors in the vasculature of spontaneously hypertensive (SHR) and normotensive Wistar Kyoto rats (WKY), of different ages was assessed in pithed rats by the use of the selective α1D-adrenoceptor antagonist BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethyl]-8-azaspiro [4.5]decane-7,9-dione dihydrochloride). BMY 7378 displaced the pressor effect of phenylephrine in young pre-hypertensive pithed SHR rats, but produced no effect in young WKY rats (dose ratio of 3.4 and 1.6, respectively), while in adult rats BMY 7378 produced a greater shift in the phenylephrine response curve than in younger animals (dose ratio of 3.2 and 6.2 in WKY and SHR, respectively). The presence of α1D-adrenoceptors in the vasculature of pre-hypertensive rats, suggests its role in the pathogenesis/maintenance of increased blood pressure. PMID:10323583

  5. Functional evidence of alpha1D-adrenoceptors in the vasculature of young and adult spontaneously hypertensive rats.

    PubMed

    Villalobos-Molina, R; López-Guerrero, J J; Ibarra, M

    1999-04-01

    The role of alpha1D-adrenoceptors in the vasculature of spontaneously hypertensive (SHR) and normotensive Wistar Kyoto rats (WKY), of different ages was assessed in pithed rats by the use of the selective alpha1D-adrenoceptor antagonist BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethyl]-8-azaspiro [4.5]decane-7,9-dione dihydrochloride). BMY 7378 displaced the pressor effect of phenylephrine in young pre-hypertensive pithed SHR rats, but produced no effect in young WKY rats (dose ratio of 3.4 and 1.6, respectively), while in adult rats BMY 7378 produced a greater shift in the phenylephrine response curve than in younger animals (dose ratio of 3.2 and 6.2 in WKY and SHR, respectively). The presence of alpha1D-adrenoceptors in the vasculature of pre-hypertensive rats, suggests its role in the pathogenesis/maintenance of increased blood pressure. PMID:10323583

  6. Effects of acute and chronic administration of fenproporex on DNA damage parameters in young and adult rats.

    PubMed

    Gonçalves, Cinara L; Rezin, Gislaine T; Ferreira, Gabriela K; Jeremias, Isabela C; Cardoso, Mariane R; Valvassori, Samira S; Munhoz, Bruna J P; Borges, Gabriela D; Bristot, Bruno N; Leffa, Daniela D; Andrade, Vanessa M; Quevedo, João; Streck, Emilio L

    2013-08-01

    Obesity is a chronic and multifactorial disease, whose prevalence is increasing in many countries. Pharmaceutical strategies for the treatment of obesity include drugs that regulate food intake, thermogenesis, fat absorption, and fat metabolism. Fenproporex is the second most commonly consumed amphetamine-based anorectic worldwide; this drug is rapidly converted in vivo into amphetamine, which is associated with neurotoxicity. In this context, the present study evaluated DNA damage parameters in the peripheral blood of young and adult rats submitted to an acute administration and chronic administration of fenproporex. In the acute administration, both young and adult rats received a single injection of fenproporex (6.25, 12.5 or 25 mg/kg i.p.) or vehicle. In the chronic administration, both young and adult rats received one daily injection of fenproporex (6.25, 12.5, or 25 mg/kg i.p.) or Tween for 14 days. 2 h after the last injection, the rats were killed by decapitation and their peripheral blood removed for evaluation of DNA damage parameters by alkaline comet assay. Our study showed that acute administration of fenproporex in young and adult rats presented higher levels of damage index and frequency in the DNA. However, chronic administration of fenproporex in young and adult rats did not alter the levels of DNA damage in both parameters of comet assay. The present findings showed that acute administration of fenproporex promoted damage in DNA, in both young and adult rats. Our results are consistent with other reports which showed that other amphetamine-derived drugs also caused DNA damage. We suggest that the activation of an efficient DNA repair mechanism may occur after chronic exposition to fenproporex. Our results are consistent with other reports that showed some amphetamine-derived drugs also caused DNA damage. PMID:23636618

  7. Influx mechanisms in the embryonic and adult rat choroid plexus: a transcriptome study

    PubMed Central

    Saunders, Norman R.; Dziegielewska, Katarzyna M.; Møllgård, Kjeld; Habgood, Mark D.; Wakefield, Matthew J.; Lindsay, Helen; Stratzielle, Nathalie; Ghersi-Egea, Jean-Francois; Liddelow, Shane A.

    2015-01-01

    The transcriptome of embryonic and adult rat lateral ventricular choroid plexus, using a combination of RNA-Sequencing and microarray data, was analyzed by functional groups of influx transporters, particularly solute carrier (SLC) transporters. RNA-Seq was performed at embryonic day (E) 15 and adult with additional data obtained at intermediate ages from microarray analysis. The largest represented functional group in the embryo was amino acid transporters (twelve) with expression levels 2–98 times greater than in the adult. In contrast, in the adult only six amino acid transporters were up-regulated compared to the embryo and at more modest enrichment levels (<5-fold enrichment above E15). In E15 plexus five glucose transporters, in particular Glut-1, and only one monocarboxylate transporter were enriched compared to the adult, whereas only two glucose transporters but six monocarboxylate transporters in the adult plexus were expressed at higher levels than in embryos. These results are compared with earlier published physiological studies of amino acid and monocarboxylate transport in developing rodents. This comparison shows correlation of high expression of some transporters in the developing brain with higher amino acid transport activity reported previously. Data for divalent metal transporters are also considered. Immunohistochemistry of several transporters (e.g., Slc16a10, a thyroid hormone transporter) gene products was carried out to confirm translational activity and to define cellular distribution of the proteins. Overall the results show that there is substantial expression of numerous influx transporters in the embryonic choroid plexus, many at higher levels than in the adult. This, together with immunohistochemical evidence and data from published physiological transport studies suggests that the choroid plexus in embryonic brain plays a major role in supplying the developing brain with essential nutrients. PMID:25972776

  8. Intestinal mast cells and eosinophils in relation to Strongyloides ratti adult expulsion from the small and large intestines of rats.

    PubMed

    Shintoku, Y; Kadosaka, T; Kimura, E; Takagi, H; Kondo, S; Itoh, M

    2013-04-01

    Mucosal mast cells (MMC) play a crucial role in the expulsion of Strongyloides ratti adults from the small intestine of mice. We reported the large intestinal parasitism of S. ratti in rats, and there has been no report on MMC in the large intestine of the natural host. We studied kinetics of MMC, together with eosinophils, in the upper and lower small intestines, caecum and colon of infected rats. Two distinct phases of mastocytosis were revealed: one in the upper small intestine triggered by stimulation of 'ordinary' adults, and the other in the colon stimulated by 'immune-resistant' adults that started parasitizing the colon around 19 days post-infection. In all 4 intestinal sites, the MMC peaks were observed 5-7 days after the number of adult worms became the maximum and the height of MMC peaks appeared to be dependent on the number of parasitic adults, suggesting an important role played by worms themselves in the MMC buildup.

  9. Effect of chronic hyperoxic exposure on duroquinone reduction in adult rat lungs.

    PubMed

    Audi, Said H; Bongard, Robert D; Krenz, Gary S; Rickaby, David A; Haworth, Steven T; Eisenhauer, Jessica; Roerig, David L; Merker, Marilyn P

    2005-11-01

    NAD(P)H:quinone oxidoreductase 1 (NQO1) plays a dominant role in the reduction of the quinone compound 2,3,5,6-tetramethyl-1,4-benzoquinone (duroquinone, DQ) to durohydroquinone (DQH2) on passage through the rat lung. Exposure of adult rats to 85% O2 for > or =7 days stimulates adaptation to the otherwise lethal effects of >95% O2. The objective of this study was to examine whether exposure of adult rats to hyperoxia affected lung NQO1 activity as measured by the rate of DQ reduction on passage through the lung. We measured DQH2 appearance in the venous effluent during DQ infusion at different concentrations into the pulmonary artery of isolated perfused lungs from rats exposed to room air or to 85% O2. We also evaluated the effect of hyperoxia on vascular transit time distribution and measured NQO1 activity and protein in lung homogenate. The results demonstrate that exposure to 85% O2 for 21 days increases lung capacity to reduce DQ to DQH2 and that NQO1 is the dominant DQ reductase in normoxic and hyperoxic lungs. Kinetic analysis revealed that 21-day hyperoxia exposure increased the maximum rate of pulmonary DQ reduction, Vmax, and the apparent Michaelis-Menten constant for DQ reduction, Kma. The increase in Vmax suggests a hyperoxia-induced increase in NQO1 activity of lung cells accessible to DQ from the vascular region, consistent qualitatively but not quantitatively with an increase in lung homogenate NQO1 activity in 21-day hyperoxic lungs. The increase in Kma could be accounted for by approximately 40% increase in vascular transit time heterogeneity in 21-day hyperoxic lungs.

  10. Site- and compartment-specific changes in bone with hindlimb unloading in mature adult rats

    NASA Technical Reports Server (NTRS)

    Bloomfield, S. A.; Allen, M. R.; Hogan, H. A.; Delp, M. D.

    2002-01-01

    The purpose of this study was to examine site- and compartment-specific changes in bone induced by hindlimb unloading (HU) in the mature adult male rat (6 months old). Tibiae, femora, and humeri were removed after 14, 21, and 28 days of HU for determination of bone mineral density (BMD) and geometry by peripheral quantitative computed tomography (pQCT), mechanical properties, and bone formation rate (BFR), and compared with baseline (0 day) and aging (28 day) controls. HU resulted in 20%-21% declines in cancellous BMD at the proximal tibia and femoral neck after 28 day HU vs. 0 day controls (CON). Cortical shell BMD at these sites was greater (by 4%-6%) in both 28 day HU and 28 day CON vs. 0 day CON animals, and nearly identical to that gain seen in the weight-bearing humerus. Mechanical properties at the proximal tibia exhibited a nonsignificant decline after HU vs. those of 0 day CON rats. At the femoral neck, a 10% decrement was noted in ultimate load in 28 day HU rats vs. 28 day CON animals. Middiaphyseal tibial bone increased slightly in density and area during HU; no differences in structural and material properties between 28 day HU and 28 day CON rats were noted. BFR at the tibial midshaft was significantly lower (by 90%) after 21 day HU vs. 0 day CON; this decline was maintained throughout 28 day HU. These results suggest there are compartment-specific differences in the mature adult skeletal response to hindlimb unloading, and that the major impact over 28 days of unloading is on cancellous bone sites. Given the sharp decline in BFR for midshaft cortical bone, it appears likely that deficits in BMD, area, or mechanical properties would develop with longer duration unloading.

  11. Repeated Ketamine Exposure Induces an Enduring Resilient Phenotype in Adolescent and Adult Rats

    PubMed Central

    Parise, Eric M.; Alcantara, Lyonna F.; Warren, Brandon L.; Wright, Katherine N.; Hadad, Roey; Sial, Omar K.; Kroeck, Kyle G.; Iñiguez, Sergio D.; Bolaños-Guzmán, Carlos A.

    2013-01-01

    Background Major Depressive Disorder (MDD) afflicts up to 10% of adolescents. However, nearly 50% of those afflicted are considered non-responsive to available treatments. Ketamine, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist has shown potential as a rapid-acting and long-lasting treatment for MDD in adults. Thus, the effectiveness and functional consequences of ketamine exposure during adolescence were explored. Methods Adolescent male rats (postnatal day [PD] 35) received two ketamine (0, 5, 10 or 20 mg/kg) injections, 4 hours apart, after exposure to day 1 of the forced swim test (FST). The next day, rats were re-exposed to the FST to assess ketamine-induced antidepressant-like responses. Separate groups were exposed to chronic unpredictable stress (CUS) to confirm findings from the FST. After these initial experiments, adolescent naïve rats were exposed to either 1 or 15 consecutive days (PD35–49) of ketamine (20 mg/kg) twice/daily. Ketamine's influence on behavioral reactivity to rewarding (i.e., sucrose preference) and aversive (i.e., elevated plus-maze, FST) circumstances was then assessed 2 months after treatment. To control for age-dependent effects, adult rats (PD75–89) were exposed to identical experimental conditions. Results Ketamine (20 mg/kg) reversed the CUS-induced depression-like behaviors in the FST. Repeated ketamine exposure resulted in anxiolytic- and antidepressant-like responses 2 months after drug exposure. None of the ketamine doses used were capable of inducing drug-seeking behaviors as measured by place preference conditioning. Conclusions Repeated ketamine exposure induces enduring resilient-like responses regardless of age of exposure. These findings point to ketamine, and its repeated exposure, as a potentially useful antidepressant during adolescence. PMID:23790225

  12. Comparative analysis of antioxidants against cadmium induced reproductive toxicity in adult male rats.

    PubMed

    Jahan, Sarwat; Khan, Mehreen; Ahmed, Shakeel; Ullah, Hizb

    2014-02-01

    The present study was conducted to compare and evaluate the potential benefits of three different antioxidants in reversing cadmium (Cd)-induced reproductive toxicity in adult male rats. Rats (n = 5) weighing 180 +/- 20 gm were divided into five groups (control, Cd, Cd + sulforaphane, Cd + vitamin E, and Cd + plant extract). Treated groups received CdCl2 (0.2 mg/kg), sulforaphane (25 µg/rat), vitamin E (75 mg/kg), and plant extract (100 mg/kg) for 15 days. Blood samples and testicular tissues were obtained for estimation of testosterone, Zn, and Cd concentration and daily sperm production/efficiency of sperm production. Cadmium exposure caused a significant decrease in final body weight (p < 0.0001). The plasma concentrations of Cd were significantly increased and Zn concentration decreased (p < 0.0001) in the Cd group as compared to the control group. The testicular concentrations of Cd were significantly increased and Zn concentration decreased (p < 0.0001) in the Cd group as compared to the control group. Cadmium exposure caused a significant decrease (p < 0.0001) in plasma testosterone concentrations and daily sperm production as compared to the control group. More significant effects were observed with Cd+sulforaphane, Cd + vitamin E, and Cd + plant extract treated groups in slashing Cd-induced toxicity. Present findings suggest that Ficus religiosa and sulforaphane are more powerful antioxidants as compared to vitamin E in reversing the oxidative stress and can have a protective role against Cd induced reproductive toxicity in adult male rats. Part of the mechanism involved in this protective role seems to be associated with the antioxidant properties of these agents in reducing reproductive damage. PMID:24156729

  13. Effect of agomelatine on adult hippocampus apoptosis and neurogenesis using the stress model of rats.

    PubMed

    Yucel, Atakan; Yucel, Nermin; Ozkanlar, Seckin; Polat, Elif; Kara, Adem; Ozcan, Halil; Gulec, Mustafa

    2016-04-01

    Agomelatine (AG) is an agonist of melatonin receptors and an antagonist of the 5-HT2C-receptor subtype. The chronobiotic properties of AG are of significant interest due to the disorganization of internal rhythms, which might play a role in the pathophysiology of depression. The present study was designed to assess the effects of the antidepressant-like activity of AG, a new antidepressant drug, on adult neurogenesis and apoptosis using stress-exposed rat brains. Over the period of 1 week, the rats were exposed to light stress twice a day for 1h. After a period of 1 week, the rats were given AG treatment at a dose of either 10mg/kg or 40mg/kg for 15 days. The animals were then scarified, and the obtained tissue sections were stained with immuno-histochemical anti-BrdU, Caspase-3, and Bcl-2 antibodies. Serum brain-derived neurotrophic factor (BDNF) concentrations were measured biochemically using a BDNF Elisa kit. Biochemical BDNF analysis revealed a high concentration of BDNF in the serum of the stress-exposed group, but the concentrations of BDNF were much lower those of the AG-treated groups. Immuno-histochemical analysis revealed that AG treatment decreased the BrdU-positive and Bcl-2-positive cell densities and increased the Caspase-3-positive cell density in the hippocampus of stress-induced rats as compared to those of the stress group. The results of the study demonstrated that AG treatment ameliorated the hippocampal apoptotic cells and increased hippocampal neurogenesis. These results also strengthen the possible relationship between depression and adult neurogenesis, which must be studied further.

  14. Effect of agomelatine on adult hippocampus apoptosis and neurogenesis using the stress model of rats.

    PubMed

    Yucel, Atakan; Yucel, Nermin; Ozkanlar, Seckin; Polat, Elif; Kara, Adem; Ozcan, Halil; Gulec, Mustafa

    2016-04-01

    Agomelatine (AG) is an agonist of melatonin receptors and an antagonist of the 5-HT2C-receptor subtype. The chronobiotic properties of AG are of significant interest due to the disorganization of internal rhythms, which might play a role in the pathophysiology of depression. The present study was designed to assess the effects of the antidepressant-like activity of AG, a new antidepressant drug, on adult neurogenesis and apoptosis using stress-exposed rat brains. Over the period of 1 week, the rats were exposed to light stress twice a day for 1h. After a period of 1 week, the rats were given AG treatment at a dose of either 10mg/kg or 40mg/kg for 15 days. The animals were then scarified, and the obtained tissue sections were stained with immuno-histochemical anti-BrdU, Caspase-3, and Bcl-2 antibodies. Serum brain-derived neurotrophic factor (BDNF) concentrations were measured biochemically using a BDNF Elisa kit. Biochemical BDNF analysis revealed a high concentration of BDNF in the serum of the stress-exposed group, but the concentrations of BDNF were much lower those of the AG-treated groups. Immuno-histochemical analysis revealed that AG treatment decreased the BrdU-positive and Bcl-2-positive cell densities and increased the Caspase-3-positive cell density in the hippocampus of stress-induced rats as compared to those of the stress group. The results of the study demonstrated that AG treatment ameliorated the hippocampal apoptotic cells and increased hippocampal neurogenesis. These results also strengthen the possible relationship between depression and adult neurogenesis, which must be studied further. PMID:26970810

  15. N-methyl-D-aspartate treatment increases circulating adrenocorticotropin and luteinizing hormone in the rat.

    PubMed

    Farah, J M; Rao, T S; Mick, S J; Coyne, K E; Iyengar, S

    1991-04-01

    Excitatory amino acids have been known to increase pituitary secretion of LH in vivo and are probably involved in the neuroendocrine regulation of the hypothalamic-pituitary-gonadal axis. We have found that systemic administration of the excitatory amino acid agonist N-methyl-D-aspartate (NMDA) evokes a transient and profound increase in circulating levels of ACTH as well. Treatment of adult male Long-Evans rats with NMDA (30 mg/kg, sc) maximally increased plasma ACTH and immunoreactive beta-endorphin from 7-15 min after injection, and levels of both remained significantly elevated until 60 min into the time course. Corresponding increases in corticosterone were observed 15 and 30 min after treatment, while LH, similar to other pituitary hormones, was increased from 7-30 min after NMDA. Stimulation of the pituitary-adrenal and pituitary-gonadal neuroendocrine axes by NMDA was monitored in subsequent studies by plasma ACTH and LH, respectively; both were increased in a dose-related manner after the administration of 3-60 mg/kg NMDA, although stimulation of ACTH (800%) was more pronounced than that of LH (200%). The increases in ACTH and LH due to NMDA were inhibited by pretreatment with the competitive NMDA antagonist (+/-)3-(2-carboxypiperazin-4- yl)propyl-1-phosphonic acid, CPP (6 and 10 mg/kg, ip, for 21 min); by contrast, dexamethasone pretreatment (50 micrograms/kg, ip, for 4 h) blocked only the NMDA-evoked increase in circulating ACTH. These findings indicate that an NMDA receptor mechanism might be involved in the acute activation of the hypothalamic-pituitary-adrenal axis in the rat.

  16. A comparison of adult and adolescent rat behavior in operant learning, extinction, and behavioral inhibition paradigms.

    PubMed

    Andrzejewski, Matthew E; Schochet, Terri L; Feit, Elizabeth C; Harris, Rachel; McKee, Brenda L; Kelley, Ann E

    2011-02-01

    Poor self-control, lack of inhibition, and impulsivity contribute to the propensity of adolescents to engage in ris