Guinea Pig Pups Research Articles

Examination of the role of adrenergic receptor stimulation in the sensitization of neuroinflammatory-based depressive-like behavior in isolated Guinea pig pups

Early-life attachment disruption appears to sensitize neuroinflammatory signaling to increase later vulnerability for stress-related mental disorders, including depression. How stress initiates this process is unknown, but studies with adult rats and mice suggest sympathetic nervous system activation and/or cortisol elevations during the early stress are key. Guinea pig pups isolated from their mothers exhibit an initial active behavioral phase characterized by anxiety-like vocalizing. This is followed by inflammatory-dependent depressive-like behavior and fever that sensitize on repeated isolation. Using strategies that have been successful in adult studies, we assessed whether sympathetic nervous system activity and cortisol contributed to the sensitization process in guinea pig pups. In Experiment 1, the adrenergic agonist ephedrine (3 or 10 mg/kg), either alone or with cortisol (2.5 mg/kg), did not increase depressive-like behavior or fever during initial isolation the following day as might have been expected to if this stimulation was sufficient to account for the sensitization process. In Experiment 2, both depressive-like behavior and fever sensitized with repeated isolation, but beta-adrenergic receptor blockade with propranolol (10 or 20 mg/kg) did not affect either of these responses or their sensitization. The high dose of propranolol did, however, reduce vocalizing. These results suggest sympathetic nervous system activation is neither necessary nor sufficient to induce the presumptive neuroinflammatory signaling underlying sensitization of depressive-like behavioral or febrile responses in developing guinea pigs. Thus, processes mediating sensitization of neuroinflammatory-based depressive-like behavior following early-life attachment disruption in this model appear to differ from those previously found to underlie neuroinflammatory priming in adults.

Sensitization of depressive-like behavior is attenuated by disruption of prostaglandin synthesis days following brief early attachment-figure isolation.

Childhood psychological trauma appears to sensitize stress-related neuroinflammatory systems to increase later vulnerability for depression and other stress-related mental disorders. Isolation of guinea pig pups from the maternal attachment figure for 3h in threatening surroundings leads to a sensitization of inflammatory-mediated, depressive-like behavior and fever during later isolations. A previous study found the non-selective COX inhibitor naproxen administered before the initial isolation moderated depressive-like behavior and its sensitization. Here, we examined effects of naproxen given following early isolation. Male and female guinea pig pups surgically implanted with telemetry devices to measure core temperature were isolated for 3h on 2 consecutive days near weaning (first isolation Day 20-24). Several days later, they began 4 consecutive days of injection with either saline vehicle or 10 or 20mg/kg naproxen prior to a third isolation in early adolescence, that is, 10 days after their first isolation. Across the first two isolations, depressive-like behavior and fever sensitized. Both doses of naproxen attenuated depressive-like behavior during the third isolation. Fever was unaffected. Results suggest prostaglandin mediation of sensitization of depressive-like behavioral, but not febrile, responses to subsequent isolation. Findings also support further study of anti-inflammatory treatments to mitigate lasting consequences of early-attachment disruption.

Presence of mother prompts dissociation of sickness behavior, fever, and hypothalamic gene expression in lipopolysaccharide-injected guinea pig pups.

During infection, sickness behaviors, such as a hunched stance with piloerection, can facilitate host resistance by supporting the generation and maintenance of fever. Fever, in turn, is mediated by hypothalamic neuroimmune signaling. Sickness behaviors, however, can also be influenced by social stimuli. In this study, guinea pig pups were injected with lipopolysaccharide to simulate a bacterial infection and then exposed to a novel, threatening environment while either with their mother or alone. We found that the presence of the mother suppressed sickness behavior, but enhanced fever, and had no measureable effect on gene expression of hypothalamic mediators of fever. This 3-way dissociation induced by the mother's presence is interpreted in terms of the differential adaptive consequences of behavioral and febrile responses for pups in this situation. The results contribute to a growing literature linking immunological and social processes.

Central oxytocin alters cortisol and behavioral responses of guinea pig pups during isolation in a novel environment

The neuropeptide oxytocin plays key roles in social bonding and stress reduction, and thus appears to be a likely mediator of maternal buffering of infant stress responses. In the guinea pig, the presence of the mother in a threatening environment buffers cortisol elevations as well as active (vocalizing) and passive (e.g. crouching) responses typical of isolation in this species; yet, effects of OT in guinea pig pups under any conditions have not been reported. Here, we examined the ability of intracerebroventricular (ICV) OT to moderate plasma cortisol levels and behavior in guinea pig pups isolated in a brightly lit, novel environment, and the ability of a highly selective OT antagonist (OTA) to reduce buffering by the mother. We found that ICV OT moderated cortisol levels and vocalizations, but increased time spent in the crouched stance, particularly in females. In addition, OT modulated other ongoing behaviors in a sex-dependent fashion. In females, OT reduced duration of walking and rearing, and increased time spent quiet, while in males OT increased duration of rearing. OTA, however, was without effect on cortisol levels or behavior. These findings, including sex differences in response, extend results from other species to the guinea pig. Further, while demonstrating that exogenous OT is sufficient to reduce biobehavioral stress responses typical of isolated guinea pig infants, the results suggest that endogenous OT is not necessary for maternal buffering of infant responses in this species.

CRF1 but not glucocorticoid receptor antagonists reduce separation-induced distress vocalizations in guinea pig pups and CRF overexpressing mouse pups. A combination study with paroxetine

RationaleGiven the large number of patients that does not respond sufficiently to currently available treatment for anxiety disorders, there is a need for improved treatment. ObjectivesWe evaluated the anxiolytic effects of corticotropin releasing factor (CRF)1 receptor antagonists and glucocorticoid receptor (GR) antagonists in the separation-induced vocalization test in guinea pigs and transgenic mice with central CRF overexpression. Furthermore, we explored effects of these drugs when given in combination with a suboptimal dose of a selective serotonin re-uptake inhibitor (SSRI). MethodsIn guinea pig pups, the CRF1 receptor antagonists CP-154,526 and DMP695, and the GR antagonists mifepristone and Org34517 (all at 2.5, 10 and 40mg/kg intraperitoneally (IP)) were tested alone or in combination with 0.63mg/kg paroxetine IP. In CRF overexpressing mouse pups and wild type littermates, effects of CP-154,526 (10, 20 and 40mg/kg subcutaneously (SC)) and mifepristone (5, 15, 45mg/kg SC) were studied alone or in combination with 0.03mg/kg paroxetine SC. ResultsCRF1 but not GR antagonists reduced the number of calls relative to vehicle in guinea pigs and mice, independent of genotype. Treatment of CRF1 receptor or GR antagonists with paroxetine had no combined effect in guinea pigs, wild type or CRF overexpressing mice. ConclusionsCurrent results indicate robust anxiolytic properties of CRF1 receptor antagonists in guinea pigs and mice overexpressing CRF, and lack thereof of GR antagonists. Although no combined treatment effects were observed, it would be interesting to study combined treatment of CRF1 receptor antagonists with SSRIs following chronic drug administration.

Maternal separation increases later immobility during forced swim in guinea pig pups: evidence for sensitization of a depressive-like state.

Early-life stress is thought to increase later vulnerability for developing depressive illness by sensitizing underlying stress-responsive systems. Guinea pig pups separated from their mother and isolated in a novel cage for 3 hr exhibit a sensitized depressive-like behavioral response when separated again the following day as well as weeks later. The behavioral response and its sensitization appear to be mediated by inflammatory factors. To determine if this sensitization is specific to the separation response or if it reflects a broader underlying depressive-like state, guinea pig pups that had either been separated for 3 hr or remained with their mothers were observed in the forced swim test the following 3 days. Earlier separation was found to increase the duration of immobility, a measure sensitive to antidepressant treatment. These results support the use of the guinea pig as a model for examining mechanisms of inflammatory-mediated sensitization of depression following stress in early life.

Maternal vitamin C deficiency does not reduce hippocampal volume and β-tubulin III intensity in prenatal Guinea pigs

Marginal vitamin C (vitC) deficiency affects 5% to 10% of adults including subpopulations such as pregnant women and newborns. Animal studies link vitC deficiency to deleterious effects on the developing brain, but exactly how the brain adapts to vitC deficiency and the mechanisms behind the observed deficits remain largely unknown. We hypothesized that vitC deficiency in utero may lead to a decreased neuronal maturation and increased cellular death giving rise to alterations of the hippocampal morphology in a guinea pig model. Brains from prenatal guinea pig pups (n=9-10 in each group) subjected to either a sufficient (918mg vitC/kg feed) or deficient (100mg vitC/kg feed) maternal dietary regimen were assessed with regards to hippocampal volume and β-tubulin isotype III staining intensity at 2 gestational time points (45 and 56). We found a distinct differential regional growth pattern of the hippocampus with a clear effect of gestational age, whereas vitC status did not affect either investigated parameters. Within hippocampal subdivisions, the overall expansion of the hippocampus from gestational day 45 to 56 was found to reside in the dentate gyrus. In conclusion, the present study found that hippocampal volume and β-tubulin isotype III intensity in the prenatal guinea pig were influenced by gestational day but not by maternal vitC intake.

The differential effects of low birth weight and Western diet consumption upon early life hepatic fibrosis development in guinea pig.

Postnatal intake of an energy dense diet, the Western diet (WD), is a strong risk factor for liver fibrosis. Recently, adverse in utero conditions resulting in low birth weight (LBW) have also been associated with postnatal fibrosis development. We assessed the independent and possible synergistic effects of placental insufficiency-induced LBW and postnatal WD consumption on liver fibrosis in early adulthood, with a specific focus on changes in inflammation and apoptosis pathways in association with fibrogenesis. Male LBW (uterine artery ablation) and normal birth weight (NBW) guinea pig pups were fed either a control diet (CD) or WD from weaning to 150 days. Significant steatosis, mild lobular inflammation, apoptosis and mild stage 1 fibrosis (perisinusoidal or portal) were evident in WD-fed offspring (NBW/WD and LBW/WD). In LBW/CD versus NBW/CD offspring, increased transforming growth factor-beta 1 and matrix metallopeptidase mRNA and sma- and Mad-related protein 4 (SMAD4) were present in conjunction with minimal stage 1 portal fibrosis. Further, connective tissue growth factor mRNA was increased and miR-146a expression decreased in LBW offspring, irrespective of diet. Independent of birth weight, WD-fed offspring exhibited increased expression of fibrotic genes as well as elevated inflammatory and apoptotic markers. Moreover, the augmented expression of collagen, type III, alpha 1 and tumor necrosis factor-alpha was associated with increased recruitment of RNA polymerase II and enhanced histone acetylation (K9) to their respective promoters. These data support a role for both LBW and postnatal WD as factors contributing to hepatic fibrosis development in offspring through distinct pathways.

Social support does not require attachment: Any conspecific tranquilizes isolated guinea-pig pups

Guinea pig pups produce typical distress whistles when isolated. Whistles’ frequency is decreased or abolished when they contact with the mother and, to a lesser degree, a sibling or even an unfamiliar female, is regained. Those non-aggressive companions were considered social support providers for reducing pup physiological stress responses and whistling rate in an unfamiliar environment. However, what would happen if the isolated pup would be in contact with an adult male, normally indifferent to pups, in such distress situation? The role of attachment and familiarity to males in promoting changes in distress responses of isolated pups was verified. Tests consisted of separating three week old pups from their family, in a familiar or an unfamiliar environment, and introducing a conspecific in the cage after one minute (mother, sibling, father or a strange male). Whistling and other behaviors were compared between the alone period and the accompanied period. Main factors were prior presence/absence of father (pups were raised with father until testing or only for the first week after birth), sex of pup, novelty of test environment and companion. It was verified that (1) all conspecifics reduced whistling rate (F4,88=77.89, p<0.001), but pups behaved differently with different conspecifics; (2) suppression of isolation induced behavior did not necessarily occur because of previous attachment (e.g., pups in the PAF condition spent more time pausing, F1,22=7.68, p<0.05, less time in passive contact with companions, F1,22=10.63, p<0.01, and ate/drank less, F1,22=6.18, p<0.05). It was concluded that the suppression of pup's isolation induced behavior by companions must not be used alone as a measure of attachment. It must be seen in an evolutionary perspective where the presence of any conspecific represents security offering self-protective behavior cues as finding a place to hide, and providing dilution effect against predation.

Adding glutathione to parenteral nutrition prevents alveolar loss in newborn Guinea pig

Bronchopulmonary dysplasia, a main complication of prematurity, is characterized by an alveolar hypoplasia. Oxidative stress is suspected to be a trigger event in this population who has a low level of glutathione, a main endogenous antioxidant, and who receives high oxidative load, particularly ascorbylperoxide from their parenteral nutrition. Hypothesis: the addition of glutathione (GSSG) in parenteral nutrition improves detoxification of ascorbylperoxide by glutathione peroxidase and therefore prevents exaggerated apoptosis and loss of alveoli.Methods: Ascorbylperoxide is assessed as substrate for glutathione peroxidase in Michaelis-Menten kinetics. Three-days old guinea pig pups were divided in 6 groups to receive, through a catheter in jugular vein, the following solutions: 1) Sham (no infusion); 2) PN(-L): parenteral nutrition protected against light (low ascorbylperoxide); 3) PN(+L): PN without photo-protection (high ascorbylperoxide); 4) 180μM ascorbylperoxide; 5) PN(+L)+10μM GSSG; 6) ascorbylperoxyde+10μM GSSG. After 4 days, lungs were sampled and prepared for histology and biochemical determinations. Data were analysed by ANOVA, p<0.05Results: The Km of ascorbylperoxide for glutathione peroxidase was 126±6μM and Vmax was 38.4±2.5nmol/min/ U. The presence of GSSG in intravenous solution has prevented the high GSSG, oxidized redox potential of glutathione, activation of caspase-3 (apoptosis marker) and loss of alveoli induced by PN(+L) or ascorbylperoxide.Conclusion: A correction of the low glutathione levels observed in newborn animal on parenteral nutrition, protects lungs from toxic effect of ascorbylperoxide. Premature infants having a low level of glutathione, this finding is of high importance because it provides hope in a possible prevention of bronchopulmonary dysplasia.

High Vitamin D Status before Conception, but Not during Pregnancy, Is Inversely Associated with Maternal Gestational Diabetes Mellitus in Guinea Pigs

Background: Whether there is a dose-dependent effect of maternal dietary cholecalciferol during pregnancy on maternal glucose tolerance is unknown. In addition, circulating osteocalcin is increased by 1,25-dihydroxyvitamin D [1,25(OH)2D] and may improve glucose homeostasis.Objective: This study was designed to test whether dietary cholecalciferol during pregnancy dose-dependently affects maternal glucose tolerance and maternal and neonatal glucose concentrations in relation to plasma osteocalcin and body composition.Methods: Female guinea pigs (n = 45; 4 mo old) were randomly assigned to 5 doses of cholecalciferol (0, 0.25, 0.5, 1, or 2 IU/g diet) fed from mating to delivery. Plasma vitamin D metabolites, minerals, and osteocalcin, and blood glucose were measured before mating, at midgestation (day 42), and at day 2 postpartum in sows and in 2-d-old pups. At day 50 of pregnancy (early third trimester), a 3-h oral-glucose-tolerance test (OGTT) (2 g/kg) was conducted. Body composition was measured before mating and at day 2 postpartum in sows and in pups.Results: A positive dose-response to dietary cholecalciferol was observed for change in maternal plasma 25-hydroxyvitamin D [25(OH)D] through pregnancy (P < 0.0001), with 1,25(OH)2D increasing by 198% in the 1-IU/g group by midgestation vs. a reduction of 43.6% in the 0-IU/g group (P = 0.05). Twenty-four (54.5%) sows had gestational diabetes mellitus (GDM) on the basis of nonfed glucose and 39 (88.6%) had GDM on the basis of 2-h OGTT glucose concentrations. There were no group differences in maternal OGTT or changes in glucose, minerals, osteocalcin concentrations, and body composition. Pre-mating 25(OH)D was inversely related to 3-h area under the curve for blood glucose from the OGTT (r = −0.31, P = 0.05). In guinea pig pups, although both 25(OH)D (P < 0.0001) and 1,25(OH)2D (P < 0.0001) followed a dose-response to maternal diet, glucose, osteocalcin, minerals, and body composition were not altered.Conclusions: Dietary vitamin D intake during pregnancy in guinea pigs does not affect the already high rate of GDM, whereas higher prepregnancy vitamin D status appears to be protective.

Pharmacological and methodological aspects of the separation-induced vocalization test in guinea pig pups; a systematic review and meta-analysis

The separation-induced vocalization test in guinea pig pups is one of many that has been used to screen for anxiolytic-like properties of drugs. The test is based on the cross-species phenomenon that infants emit distress calls when placed in social isolation.Here we report a systematic review and meta-analysis of pharmacological intervention in the separation-induced vocalization test in guinea pig pups. Electronic databases were searched for original research articles, yielding 32 studies that met inclusion criteria. We extracted data on pharmacological intervention, animal and methodological characteristics, and study quality indicators.Meta-analysis showed that the different drug classes in clinical use for the treatment of anxiety disorders, have comparable effects on vocalization behaviour, irrespective of their mechanism of action. Of the experimental drugs, nociception (NOP) receptor agonists proved very effective in this test. Analysis further indicated that the commonly used read-outs total number and total duration of vocalizations are equally valid. With regard to methodological characteristics, repeated testing of pups as well as selecting pups with moderate or high levels of vocalization were associated with larger treatment effects. Finally, reporting of study methodology, randomization and blinding was poor and Egger’s test for small study effects showed that publication bias likely occurred.This review illustrates the value of systematic reviews and meta-analyses in improving translational value and methodological aspects of animal models. It further shows the urgent need to implement existing publication guidelines to maximize the output and impact of experimental animal studies.

Naproxen attenuates sensitization of depressive-like behavior and fever during maternal separation

Early life stress can increase susceptibility for later development of depressive illness though a process thought to involve inflammatory mediators. Isolated guinea pig pups exhibit a passive, depressive-like behavioral response and fever that appear mediated by proinflammatory activity, and which sensitize with repeated separations. Treatment with an anti-inflammatory can attenuate the behavioral response during the initial separation and separation the following day. Here we used the cyclooxygenase inhibitor naproxen to examine the role of prostaglandins in mediating the depressive-like behavior and core body temperature of young guinea pigs during an initial separation, separation the next day, and separation 10days after the first. The passive, depressive-like behavior as well as fever sensitized with repeated separation. Three days of injection with 14mg/kg of naproxen prior to the initial separation reduced depressive-like behavior during all three separations. A 28mg/kg dose of naproxen, however, had minimal effect on behavior. Fever during the early separations was moderated by naproxen, but only at the higher dose. These results suggest a role of prostaglandins in the behavioral and febrile response to maternal separation, and particularly in the sensitization of depressive-like behavior following repeated separation.

Selective social buffering of behavioral and endocrine responses and Fos induction in the prelimbic cortex of infants exposed to a novel environment.

In mammals, the presence of the mother can reduce or "buffer" stress responses of her young in threatening conditions. We compared the effect of the mother, a familiar littermate, and an unfamiliar adult male on three classes of response shown by guinea pig pups in a novel environment: short latency active behaviors, particularly vocalizing; slower developing passive behaviors that appear mediated by inflammatory mechanisms; and hypothalamic-pituitary-adrenal activity. We also examined Fos induction in the prelimbic cortex, a region hypothesized to mediate buffering effects. Only the mother significantly suppressed all classes of behavior. The greatest selectivity was observed for passive behavioral responses. Contrary to expectations, the adult male reduced plasma cortisol levels of pups as effectively as did the mother. The presence of the male also resulted in increased Fos induction in the prelimbic cortex and high levels of social interaction. Maternal buffering was not associated with prelimbic activity. These results confirm the ability of the mother to reduce active behavioral and HPA responses and suggest a specific maternal buffering effect on the later developing passive behavioral responses. The findings also demonstrate an unexpected ability of adult males to reduce HPA responses and raise the possibility that different social partners buffer HPA activity through different underlying processes.

Low Birth Weight Male Guinea Pig Offspring Display Increased Visceral Adiposity in Early Adulthood

Uteroplacental insufficiency (UPI)-induced intrauterine growth restriction (IUGR) predisposes individuals to adult visceral obesity. We postulated that low birth weight (LBW) offspring, from UPI-induced IUGR pregnancies, would display a visceral adipose lipogenic molecular signature involving altered gene expression, phosphorylation status of proteins of the lipid synthesis pathway and microRNA (miR) expression profile, occurring in association with increased visceral adiposity. Normal birth weight (NBW) and LBW (obtained by uterine artery ablation) male guinea pig pups were fed a control diet from weaning to 145 days and sacrificed. Despite being lighter at birth, LBW pups displayed body weights similar to NBW offspring at 145 days. At this age, which represents young adulthood, the relative weights of LBW epididymal white adipose tissue (EWAT) and lipid content were increased; which was consistent with adipocyte hypertrophy in the LBW offspring. Additionally, the mRNA expression of lipid synthesis-related genes including acetyl-CoA carboxylase 1 (ACC1), diglyceride acyltransferase 2 (DGAT2) and peroxisome proliferator-activated receptor gamma 1 (PPARγ1), was increased in LBW EWAT. Further, LBW EWAT displayed decreased phospho-ACC (Ser79) and phospho-PPARγ (Ser273) proteins. Moreover, the mRNA expression of hormone-sensitive lipase (HSL) and fatty acid binding protein 4 (FABP4), both involved in promoting adipose lipid storage, was increased in LBW EWAT. Finally, miR-24 and miR-103-2, miRs related to adipocyte development, were both increased in LBW EWAT. These findings indicate that, following an adverse in utero environment, lipid synthesis-related genes and miR expression, along with phosphorylation status of key regulators of lipid synthesis, appear to be chronically altered and occur in association with increased visceral adiposity in young adult IUGR male offspring.

Characterization of a novel vasopressin V1b receptor antagonist, V1B-30N, in animal models of anxiety-like and depression-like behavior

Overactivity of the hypothalamic–pituitary–adrenal (HPA) axis has been linked to affective disorders such as anxiety and depression. Dampening HPA activity has, therefore, been considered as a possible means of treating affective disorders. Given the important role of vasopressin in modulating the HPA axis, one strategy has focused on inhibiting activity of the vasopressin 1b (V1b) receptor. In animals, V1b receptor antagonists reduce plasma stress hormone levels and have been shown to have an anxiolytic-like effect. Recently, V1B-30N was identified as a highly potent V1b receptor antagonist with selectivity over other vasopressin receptors, which is evaluated here in rodent models of anxiety-like and depression-like behaviors. V1B-30N (1–30mg/kg, IP) dose-dependently reduced separation-induced vocalizations in rat pups without producing any sedative effects in the animals. Similarly, V1B-30N (3–30mg/kg, IP) dose-dependently reduced separation-induced vocalizations in guinea pig pups. In a conflict assay, conditioned lick suppression, V1B-30N (3–30mg/kg, IP) increased punished licking. To assess antidepressive-like properties, V1B-30N (1–30mg/kg) was tested in the mouse and rat forced-swim tests but was found to be inactive. These results are consistent with previous findings with other V1b antagonists, which suggest that acute pharmacological antagonism of the V1b receptor has anxiolytic-like but not antidepressant-like properties.

Changes in Neuroactive Steroid Concentrations After Preterm Delivery in the Guinea Pig

Preterm birth is a major cause of neurodevelopmental disorders. Allopregnanolone, a key metabolite of progesterone, has neuroprotective and developmental effects in the brain. The objectives of this study were to measure the neuroactive steroid concentrations following preterm delivery in a neonatal guinea pig model and assess the potential for postnatal progesterone replacement therapy to affect neuroactive steroid brain and plasma concentrations in preterm neonates. Preterm (62-63 days) and term (69 days) guinea pig pups were delivered by cesarean section and tissue was collected at 24 hours. Plasma progesterone, cortisol, allopregnanolone, and brain allopregnanolone concentrations were measured by immunoassay. Brain 5α-reductase (5αR) expression was determined by Western blot. Neurodevelopmental maturity of preterm neonates was assessed by immunohistochemistry staining for myelination, glial cells, and neurons. Brain allopregnanolone concentrations were significantly reduced after birth in both preterm and term neonates. Postnatal progesterone treatment in preterm neonates increased brain and plasma allopregnanolone concentrations. Preterm neonates had reduced myelination, low birth weight, and high mortality compared to term neonates. Brain 5αR expression was also significantly reduced in neonates compared to fetal expression. Delivery results in a loss of neuroactive steroid concentrations resulting in a premature reduction in brain allopregnanolone in preterm neonates. Postnatal progesterone therapy reestablished neuroactive steroid levels in preterm brains, a finding that has implications for postnatal growth following preterm birth that occurs at a time of neurodevelopmental immaturity.

Comparative Analysis of Detection Methods for Congenital Cytomegalovirus Infection in a Guinea Pig Model

To assess the validity of the guinea pig as a model for congenital cytomegalovirus (CMV) infection by comparing the effectiveness of detecting the virus by real-time polymerase chain reaction (PCR) in blood, urine, and saliva. Case-control study. Academic research. Eleven pregnant Hartley guinea pigs. Blood, urine, and saliva samples were collected from guinea pig pups delivered from pregnant dams inoculated with guinea pig CMV. These samples were then evaluated for the presence of guinea pig CMV by real-time PCR assuming 100% transmission. Thirty-one pups delivered from 9 inoculated pregnant dams and 8 uninfected control pups underwent testing for guinea pig CMV and for auditory brainstem response hearing loss. Repeated-measures analysis of variance demonstrated no statistically significantly lower weight for the infected pups compared with the noninfected control pups. Six infected pups demonstrated auditory brainstem response hearing loss. The sensitivity and specificity of the real-time PCR assay on saliva samples were 74.2% and 100.0%, respectively. The sensitivity of the real-time PCR on blood and urine samples was significantly lower than that on saliva samples. Real-time PCR assays of blood, urine, and saliva revealed that saliva samples show high sensitivity and specificity for detecting congenital CMV infection in guinea pigs. This finding is consistent with recent screening studies in human newborns. The guinea pig may be a good animal model in which to compare different diagnostic assays for congenital CMV infection.

Maternal inhibition of infant behavioral response following isolation in novel surroundings and inflammatory challenge

During isolation in a novel environment, guinea pig pups gradually begin to display passive behavior that appears to be mediated by proinflammatory activity, that is, "sickness behavior.". Administration of substances that increase proinflammatory activity [corticotropin-releasing factor (CRF), lipopolysaccharide (LPS)] prior to isolation induces passive behavior from the beginning of the isolation episode. Here, we show that reunion with the mother in the novel environment rapidly and potently suppresses the passive behavior of isolated pups (Experiment 1); inhibits the passive behavior of pups administered CRF (10 µg, subcutaneous; Experiment 2); and inhibits the passive behavior of male, though not female, pups administered LPS (250 µg/kg, intraperitoneal; Experiment 3). Together these findings suggest that the presence of the mother either recruits other processes that moderate the impact of proinflammatory processes on brain mechanisms mediating the passive response or initiates compensatory mechanisms that counter the effect of proinflammatory activity. Further, the results suggest that for physically ill animals of social species, the adaptive advantage that accrues from maintaining normal social interactions may sometimes outweigh the advantage gained by engaging in sickness behavior.

Maternal supplementation with dietary arachidonic and docosahexaenoic acids during lactation elevates bone mass in weanling rat and guinea pig offspring even if born small sized

Whether post-natal long chain polyunsaturated fatty acids (LCPUFA) elevates bone mineral content (BMC) of small and normal neonates was studied using pregnant rats and guinea pigs fed a control (C) diet or low protein (LP) diet to induce small neonates followed by C or LCPUFA diets during lactation. Measurements (days 3 and 21 post-partum) included BMC and density (BMD) plus bone metabolism. In rats LP reduced birth weight but at day 21 elevated weight and whole body BMC; LCPUFA enhanced spine BMC, tibia BMC and BMD and whole body BMD. In guinea pig pups, at days 3 and 21, LP reduced weight, whole body and regional BMC and BMD whereas LCPUFA reduced day 3 osteocalcin and elevated day 21 spine BMD. LCPUFA minimized loss of whole body BMC in dams and elevated osteocalcin in sows. LCPUFA during lactation enhances bone in normal and small neonates without compromising maternal bone.