Prepubescent Rats Research Articles

Sex Differences in the Absorption, Disposition, Metabolism, and Excretion of Grape Seed Proanthocyanidins in Prepubescent Rats.

The absorption, disposition, metabolism, and excretion (ADME) of phenolic compounds are key factors in determining their bioactivity. The group demonstrates that the ADME of a Grape Seed Proanthocyanidin Extract (GSPE) depends on sex in adult rats and specifically, methylated metabolites are only quantified in brain male adult rats. The aim of this study is to determine whether these differences exist before puberty. Prepubescent 4-week-old male and female Wistar rats are administered GSPE at a dose of 1000mgkg-1. Plasma, liver, mesenteric white adipose tissue (MWAT), brain, and kidneys are extracted excised 2h after GSPE administration, and the PAs metabolite profile is studied by HPLC-ESI-MS/MS. Moreover, plasma estradiol and brain and liver catechol-O-methyltransferase (COMT) protein levels are also studied. Results showed that there are no differences in plasma and brain among sexes and only differences are observed in liver, MWAT, and kidney with individual metabolites. This agrees with the lack of differences in estradiol and COMT levels among sexes. However, the ADME of PAs metabolites is higher in male rats. The results demonstrate lack of sex-dependence in metabolite profile in prepubescent rats, suggesting that sex differences in the metabolism of GSPE occur due to puberty.

Sex and age affect depot expression of Ca2+ channels in rat white fat adipocytes.

White adipose tissue (WAT) requires extracellular Ca2+ influx for lipolysis, differentiation, and expansion. This partly occurs via plasma membrane Ca2+ voltage-dependent channels (CaVs). However, WFA exists in different depots whose function varies with age, sex, and location. To explore whether their CaV expression profiles also differ we used RNAseq and qPCR on gonadal, mesenteric, retroperitoneal, and inguinal subcutaneous fat depots from rats of different ages and sex. CaV expression was found dependent on age, sex, and WFA location. In the gonadal depots of both sexes a significantly lower expression of CaV1.2 and CaV1.3 was seen for adults compared to pre-pubescent juveniles. A lower level of expression was also seen for CaV3.1 in adult male but not female gonadal WFA, the latter of whose expression remained unchanged with age. Relatively little expression of CaV3.2 and 3.2 was observed. In post-pubescent inguinal subcutaneous fat, where the third and fourth mammary glands are located, CaV3.1 was decreased in males but increased in females - thus suggesting that this channel is associated with mammogenesis; however, no difference in intracellular Ca2+ levels or adipocyte size were noted. For all adult depots, CaV3.1 expression was larger in females than males - a difference not seen in pre-pubescent rats. These observations are consistent with the changes of CaV3.1 expression seen in 3T3-L1 cell differentiation and the ability of selective CaV3.1 antagonists to inhibit adipogensis. Our results show that changes in CaV expression patterns occur in fat depots related to sexual dimorphism: reproductive tracts and mammogenesis.

482 Traumatic Brain Injury and Hemorrhage in a Juvenile Rat Model of Polytrauma Leads to Immunosuppression and Splenic Alterations

INTRODUCTION: Traumatic brain injury (TBI) is a common cause of morbidity and mortality for which there are no pharmacotherapeutic agents. We have previously shown, with clinical data and in an animal model, that TBI with a concurrent extra-cranial injury can reliably lead to post-injury immunosuppression. METHODS: To assess the clinical relevance of our combined model, we examined lungs for evidence of spontaneous bacterial colonization. Prepubescent (28 day old) rats were injured with a moderately severe controlled cortical impact model and then had 25% blood volume removed by arteriotomy. Blood and spleen samples at post-injury day 1 were incubated with T or B cell immunostimulant and were examined for IFN-G production using an Eli-Spot assay. Spleen samples were examined at this timepoint for apoptosis using Annexin V staining. Lungs were also harvested and plated on blood agar to examine spontaneous bacterial colonization. RESULTS: Stimulation of whole blood samples and spleen with PMA at post-injury day 1 were associated with significant decreases in IFN-G-positive cells/million, as compared with samples from sham animals. As compared to sham, spleen samples from injured animals showed a marked increase in splenocyte apoptosis in the white pulp of the spleen. Lung samples, plated on blood agar, showed a 300% increase in colonies per plate in injured animals. CONCLUSION: These data add to a growing body of literature suggesting that severe trauma can lead to immunosuppression. Our findings further suggest a potential role for the spleen in altering leukocyte function following injury.

Preventive treatment with fish oil facilitates the antidepressant-like effect of antidepressant drugs in type-1 diabetes mellitus rats: Implication of serotonergic system

Treating depression associated with type-1 diabetesmellitus(T1DM) is a major clinical challenge. Fish oil (FO), composed mostly of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), has been pointed out as quite promising for the treatment of depression given its neuroprotective property. Although DHA and EPA exert several physiological actions, DHA is known to play a critical role in postnatal brain development. This study aimed to investigate the effect of preventive treatment with FO (with more DHA in the composition) alone or associated with antidepressant drugs on depression-like behaviors and brain monoamines levels of juvenile induced-T1DM rats. Thus, prepubescent rats were submitted to a prolonged treatment with vehicle (VEH) or FO (50% of DHA and 20% EPA) starting 4 weeks before the induction of experimental T1DM (on day 28) by streptozotocin. When combined, the treatment with vehicle, fluoxetine (FLX, a selective serotonin reuptake inhibitor) or imipramine (IMI, a tricyclic antidepressant) started at week 6 (day 42) and lasted for 2 weeks (until day 56). The behavioral tests were conducted on days 55 and 56, followed by hippocampal and prefrontal cortex dissection for neurochemical analyses. Our results showed that induced-T1DM rats pretreated with FO showed a significant increase of EPA and DHA in plasma, indicative of an increase in the systemic availability of these acids. As previously observed, induced-T1DM rats presented increased immobility and decreased swimming and climbing frequencies in the modified forced swimming test, indicative of depressive-like behavior. Only the combined treatment – FO plus antidepressants (FLX or IMI – both in the highest dose) - was able to induce a significant improvement of depressive-like behaviors. Here, it is noteworthy that swimming behavior has been associated with an increase in serotonergic neurotransmission. Interestingly, our data showed that the combined treatment (FO + antidepressants - including the ineffective dose of FLX) was able to increase the swimming of animals more significantly compared to animals not pretreated with FO. In addition, confirming these assumptions, the decreased 5-HT levels in the hippocampus from induced-T1DM rats were increased after treatment with FLX (highest dose) or IMI (both doses), being this increase more pronounced in animal pretreated with FO. Intriguingly, in these animals pretreated with FO, the ineffective dose of FLX in association with FO was able to increase the levels of 5-HT. The decreased hippocampal levels of noradrenaline were increased only after IMI treatment, not being influenced by FO pretreatment. In conclusion, ours results pointed out that the choice of the DHA/EPA ratio may be an important factor to be considered for the FO antidepressant-like effectper se,but the FO treatment in this composition associated with the antidepressant drugs - especially that ones that increase preferentially the availability of 5-HT -, may represent a better alternative of treatment to individuals with T1DM-associated depression.

Traumatic brain injury and hemorrhage in a juvenile rat model of polytrauma leads to immunosuppression and splenic alterations

BackgroundTraumatic brain injury (TBI) is a common cause of morbidity and mortality. We have previously shown that TBI with a concurrent extra-cranial injury reliably leads to post-injury suppression of the innate immune system, but the impact of this injury on the adaptive immune system is unknown. We present data showing that combined injury reduced immune response as assayed in both blood and spleen samples and that these changes parallel apoptosis in the spleen. To assess the clinical relevance of these changes, we examined lungs for spontaneous bacterial colonization. MethodsFor these studies, prepubescent (28 day old) rats were injured using a controlled cortical impact model and then 25% blood volume removal by arteriotomy, and injured animals were compared with sham injured animals. Blood and spleen samples at post-injury day 1 were incubated with or without immunostimulant and examined for IFN-γ production using an Eli-Spot assay. Spleen samples were also examined for apoptosis using Annexin V staining, and lungs were harvested and plated on blood agar to examine for spontaneous bacterial colonization. ResultsStimulations of whole blood and spleen samples with phorbol 12-myristate 13-acetate/ionomycin (PMA/I) at post-injury day 1 were associated with significant decreases in IFN-γ-positive cells/million in injured animals. Stimulation of whole blood with either PMA/I or pokeweed mitogen led to reduced tumor necrosis factor alpha production. Spleen from injured animals showed a marked increase in apoptosis. Lung samples showed a 300% increase in colonies per plate in injured animals. ConclusionsThese data suggest that the combined injury can lead to adaptive immunosuppression, and our findings further suggest a potential role for the spleen in altering leukocyte function following injury.

Low and high doses of oxandrolone promote pathological cardiac remodeling in young male rats

Oxandrolone (OXA) used in clinical practice, however, its misuse is frequent, including by adolescents pursuing an aesthetic goal. However, the impacts of noxious doses on the cardiovascular system remain unknown. AimTo investigate cardiac effects of OXA in low (LD) and high (HD) doses. MethodsMale Wistar prepubescent rats were separated into 3 experimental groups: control (CON), LD, and HD. Only the CON group received the carrier (carboxymethylcellulose, 0.5%), while the LD and HD groups received, respectively, 2.5 and 37.5 mg/kg/day of OXA via gavage for 4 weeks. The hemodynamic parameters (+dP/dtmax, −dP/dtmin, and Tau) and cardiac autonomic tonus were assessed. Hearts were retrieved for histological analyses and oxidative stress evaluation. Expression levels of calcium-handling proteins were measured by western blot. ResultsThe OXA treatment changed neither the cardiac contractility nor the cardiac autonomic tonus. However, cardiac hypertrophy, collagen deposition, and increased angiotensin-converting enzyme (ACE) expression were observed in a dose-dependent way. Also, the p-phospholamban (p-PLB)/PLB ratio was observed to decrease and increase, respectively, in the LD and HD groups; the sarcoplasmic/endoplasmic reticulum calcium ATPase 2a (SERCA2a)/PLB ratio being higher in both groups. OXA increased SOD1 expression and decreased catalase expression only in the LD group, and protein oxidation was increased in HD. ConclusionBoth doses of OXA could promote pathological cardiac remodeling, probably via increased ACE, and these effects were exacerbated in the HD treatment, but cardiac contractility was not affected regardless of the dose.

Impact of Maternal Sleep Deprivation and Caffeine Consumption on Neurodevelopmental and Behavioural Outcomes in Young Rats

Caffeine is a neurostimulant, which has been shown to be both cognitive‐enhancing and sleep‐disrupting. Several reports agree that caffeine and sleep deprivation have opposing effects on behaviours, including cogntive and depressive behaviours. Therefore, this study was designed to evaluate the neurodevelopmental and behavioural outcomes following prenatal and postnatal caffeine treatment and chronic sleep deprivation in rats. Pregnant Long‐Evans rats were sleep‐deprived 8 h/day in the last trimester of gestation using the platform‐over‐water sleep deprivation model; and treated orally with 120 mg/kg of caffeine from gestation day 8 and throughout lactation. Learning and memory, social, anxiety‐like and depressive‐like behaviours were assessed in the prepubescent rats (Postnatal Date 35). The young rats exhibited a higher anxiety level, as revealed by higher open field entry frequencies. They performed poorly in the novel object recognition test, and displayed abnormal sociability and social novelty in the social tests. Additionally, there was decreased hippocampal serotonergic activity and a marked reduction in synaptic protein expression in the CA1 hippocampal region, the prefrontal cortex and amygdala. Taken together, this study suggests that prenatal and postnatal sleep deprivation and caffeine consumption can interfere with brain development and thus impact behavioural outcomes, which could increase susceptibility to neurological disorders in adulthood.

Anti-Estrogenic Activity of Guajadial Fraction, from Guava Leaves (Psidium guajava L.).

The research of natural products has allowed for the discovery of biologically relevant compounds inspired by plant secondary metabolites, which contributes to the development of many chemotherapeutic drugs used in cancer treatment. Psidium guajava leaves present a diverse phytochemical composition including flavonoids, phenolics, meroterpenoids, and triterpenes as the major bioactive constituents. Guajadial, a caryophyllene-based meroterpenoid, has been studied for potential anticancer effects tested in tumor cells and animal experimental models. Moreover, guajadial has been reported to have a mechanism of action similar to tamoxifen, suggesting this compound as a promisor phytoestrogen-based therapeutic agent. Herein, the anti-estrogenic action and anti-proliferative activity of guajadial is reported. The enriched guajadial fraction was obtained by sequential chromatographic techniques from the crude P. guajava dichloromethane extract showing promising anti-proliferative activity in vitro with selectivity for human breast cancer cell lines MCF-7 and MCF-7 BUS (Total Growth Inhibition = 5.59 and 2.27 µg·mL−1, respectively). Furthermore, evaluation of anti-estrogenic activity in vivo was performed demonstrating that guajadial enriched fraction inhibited the proliferative effect of estradiol on the uterus of pre-pubescent rats. These results suggest a relationship between anti-proliferative and anti-estrogenic activity of guajadial, which possibly acts in tumor inhibition through estrogen receptors due to the compounds structural similarity to tamoxifen.

Corticosterone Induces Depressive-Like Behavior in Female Peri-Pubescent Rats, but Not in Pre-Pubescent Rats

Background There are no data on the effect of exogenous corticosterone on depressive-like behavior in juvenile rats. Furthermore, it has not been tested whether the effects of corticosterone in female rats is different before or after puberty. Objective We tested the effect of corticosterone treatment on female pre- and peri-pubescent juvenile rats on depressive-like behavior. Methods Female juvenile rats were divided into pre-pubescent (post-natal day 7–27) or peri-pubescent (post-natal day 28–48) groups and administered daily corticosterone (40 mg kg−1 day−1) for 21 days. Depressive-like behavior was assessed using a modified forced swim test and the sucrose preference test. After behavioral assessment, brains were analyzed to determine if there were changes in cell proliferation and newborn neuron survival in the dentate gyrus of the dorsal hippocampus. Results Chronic corticosterone treatment did not affect behavior or neurogenesis in female pre-pubescent juvenile rats. However, female peri-pubescent rats injected with corticosterone showed increased depressive-like behavior as well as a decrease in cell proliferation in the subgranular zone. Furthermore, there was an inverse correlation between time spent immobile in the forced swim test and cell proliferation in the granule cell layer in peri-pubescent rats. Conclusions Corticosterone induces depressive-like behavior in peri-pubescent, but not in pre-pubescent female rats. Finally, our results suggest that depressive-like behavior may be associated with a decrease in hippocampal cell proliferation in female peri-pubescent rats.

Innate immune suppression after traumatic brain injury and hemorrhage in a juvenile rat model of polytrauma

Traumatic injury in children is known to cause immune suppression. Polytrauma involving a traumatic brain injury (TBI) may increase this degree of immune suppression, which increases the risk of developing nosocomial infections, potentially causing secondary brain injury and worsening patient outcomes. Despite the high prevalence of polytrauma with TBI in children, mechanisms of immune suppression following such injuries remain poorly understood. Here, we used a combined animal injury model of TBI and hemorrhage to assess immune function after polytrauma. Pre-pubescent rats were injured using a prefrontal controlled cortical impact method and a controlled hemorrhage by femoral arteriotomy. Immune function was measured by whole blood ex-vivo tumor necrosis factor alpha production capacity following incubation with lipopolysaccharide, measuring the percentage of monocytes by flow cytometry, and by examining concentrations of plasma cytokines. The degree of brain injury was sufficient to produce deficits in spatial memory testing (Barnes maze). Both hemorrhage and TBI with hemorrhage (combined injury) reduced several of the measured plasma cytokines, as compared with TBI alone. The combined injury correlated with reduced concentration of monocytes and reduced tumor necrosis factor alpha production capacity at post-injury day 1. These results demonstrate that this animal model can be used to study post-injury immune suppression.

Структурно-функциональная характеристика нервной, эндокринной систем и состава микрофлоры ободочной кишки у крыс вистар в периоды новорожденности и препубертата

Структурно-функциональная характеристика нервной, эндокринной систем и состава микрофлоры ободочной кишки у крыс вистар в периоды новорожденности и препубертата

Participation of COX-1 and COX-2 in the contractile effect of phenylephrine in prepubescent and old rats.

Vascular reactivity can be influenced by the vascular region, animal age, and pathologies present. Prostaglandins (produced by COX-1 and COX-2) play an important role in the contractile response to phenylephrine in the abdominal aorta of young rats. Although these COXs are found in many tissues, their distribution and role in vascular reactivity are not clear. At a vascular level, they take part in the homeostasis functions involved in many physiological and pathologic processes (e.g., arterial pressure and inflammatory processes). The aim of this study was to analyze changes in the contractile response to phenylephrine of thoracic/abdominal aorta and the coronary artery during aging in rats. Three groups of rats were formed and sacrificed at three distinct ages: prepubescent, young and old adult. The results suggest that there is a higher participation of prostanoids in the contractile effect of phenylephrine in pre-pubescent rats, and a lower participation of the same in old rats. Contrarily, there seems to be a higher participation of prostanoids in the contractile response of the coronary artery of older than pre-pubescent rats. Considering that the changes in the expression of COX-2 were similar for the three age groups and the two tissues tested, and that expression of COX-1 is apparently greater in older rats, COX-1 and COX-2 may lose functionality in relation to their corresponding receptors during aging in rats.

Possible cause for altered spatial cognition of prepubescent rats exposed to chronic radiofrequency electromagnetic radiation.

The effects of chronic and repeated radiofrequency electromagnetic radiation (RFEMR) exposure on spatial cognition and hippocampal architecture were investigated in prepubescent rats. Four weeks old male Wistar rats were exposed to RF-EMR (900MHz; SAR-1.15W/kg with peak power density of 146.60μW/cm(2)) for 1h/day, for 28days. Followed by this, spatial cognition was evaluated by Morris water maze test. To evaluate the hippocampal morphology; H&E staining, cresyl violet staining, and Golgi-Cox staining were performed on hippocampal sections. CA3 pyramidal neuron morphology and surviving neuron count (in CA3 region) were studied using H&E and cresyl violet stained sections. Dendritic arborization pattern of CA3 pyramidal neuron was investigated by concentric circle method. Progressive learning abilities were found to be decreased in RF-EMR exposed rats. Memory retention test performed 24h after the last training revealed minor spatial memory deficit in RF-EMR exposed group. However, RF-EMR exposed rats exhibited poor spatial memory retention when tested 48h after the final trial. Hirano bodies and Granulovacuolar bodies were absent in the CA3 pyramidal neurons of different groups studied. Nevertheless, RF-EMR exposure affected the viable cell count in dorsal hippocampal CA3 region. RF-EMR exposure influenced dendritic arborization pattern of both apical and basal dendritic trees in RF-EMR exposed rats. Structural changes found in the hippocampus of RF-EMR exposed rats could be one of the possible reasons for altered cognition.

Valoración de la dosis efectiva media y sensibilidad estacional en el bufo spinulosus, usando standard internacional de gonadotrofina corionica

Usando por primera vez en nuestro país standard internacional de gonadotrofina coriónica, hemos observado modificaciones estacionales de la sensibilidad al desprendimiento de espermatozoides en el sapo común de Lima, en forma similar a la que presentan diversas especies de batracios en otros países. Los resultados hemos apreciado por la dosis efectiva teórica en U.I. para cada estación, encontrando valores D. E. 50 ó D.E.M. entre 9 y 15 U.I., con sensibilidad máxima en primavera, decreciente en verano y mínima en otoño, para volver a aumentar en invierno. Aplicando estos informes, como se comprende, se facilita en nuestro medio la determinación cuantitativa de la gonadotrofina coriónica en unidades internacionales, usando el Bufo spinulosus y con ayuda de las curvas dosis-respuestas para cada estación representadas en un diagrama, sin importar la época del año en que se trabaje. Con todo, creemos oportuno establecer que sólo es válido el método para las titulaciones en sangre y orina que se realicen en Lima; si hay la intención de aplicarlo en otras regiones del país, previamente conviene valorar en cada zona la sensibilidad específica del animal reactivo del lugar para evitar un posible error de cálculo. Por otra parte, nuestro animal de laboratorio ha resultado más sensible que sus congéneres de otros países y comparable a la que presenta la coneja, aunque menor a la rata impúber. Por ello, juzgamos conveniente usar el Bufo spinulosus para determinaciones cuantitativas cuando se busquen niveles altos de gonadotrofinas coriónicas, en tanto que no es apropiado para niveles bajos.

Progressive Obesity in Female Rats from Synergistic Interactions between Drugs and Whole Body Application of Weak, Physiologically Patterned Magnetic Fields

Prepubescent female rats treated with the atypical neuroleptic acepromazine but not ketamine, prazosin, or doxepin, after lithium/pilocarpine-induced seizures gradually became obese over their lifetimes if spontaneous seizures developed. Mild increases in weight gain were induced when prepuberal females were given pilocarpine and acepromazine while being exposed briefly (1.5 hr) to a frequency-modulated magnetic field known to induce seizures. Weekly (1.5 hr) exposures to physiologically-patterned magnetic fields over 36 wks had no effect on weight gain while continuous periseizure exposure to 50 Hz fields above about 1 μT facilitated mild weight gains and protracted aggression. Perinatal exposure to a very weak, a 7 Hz magnetic field or a nitric oxide inhibitor retarded the weight gain induced by the obesity procedure. These results indicate that synergisms during a single episode between neuronal electrical lability and pharmacological states can initiate a process of weight gain that progresses to extreme obesity. We suggest that at least a component of the global “epidemic of obesity” could be related to a synergism between the insidious emergence of amplitude modulations within biologically compatible electromagnetic frequencies from the proliferation of communication systems and the pervasive utilization of pharmacology to treat transient disorders of ontogeny within the human population.

Morphofunctional Modifications of Cells of the Preoptic Hypothalamic Nucleus of Prepubescent Rats under Conditions of Stimulation and Blocking of the α-Adrenergic and Kisspeptinergic Systems

In experiments on prepubescent (one-month-old) male albino rats, we studied the effects of pharmacological blockade and activation of kisspeptinergic and α-adrenergic systems on neurocytes and astrocytes of the preoptic hypothalamic nucleus. Intracerebroventricular injection of kisspeptin induced activation of the processes of synthesis of proteins in neurons and astrocytes of this nucleus, which was manifested in significantly greater mean values of cross-section areas of the nuclei of these cell units. Injections of a blocker of kisspeptin receptors, Р-234, inhibited synthetic activity in neurons but not in astrocytes. Mezaton intensely activated the above-mentioned activity in cells of both types; such activation could not be eliminated completely by simultaneous injection of the kisspeptin antagonist Р-234. Prazosin suppressed synthetic processes in neurons but not in astrocytes. In the case of combined introduction of prazosin and kisspeptin, the effect of inhibition of protein synthesis in neurons was significantly weakened but could not be eliminated completely; in astrocytes, the functional activity increased. We discuss the mechanisms of action of the α-adrenergic and kisspeptinergic systems on production of gonadotropin-releasing hormone (gonadoliberin) by cells of the preoptic hypothalamic nucleus and the actions of these events on the functioning of the reproductive system.

Tickling in juvenile but not adult female rats conditions sexual partner preference

Female rats display a conditioned partner preference for males that bear odors paired with different types of rewarding unconditioned stimuli (UCS). Here we examined whether tickling constitutes a rewarding UCS that supports the development of partner preferences. In Experiment 1, we tested the possibility that odors associated with a tickling UCS in prepubescent rats would induce a conditioned partner preference in adulthood. Two groups were formed with 31-day-old, single-housed females, tickled for 6min daily for 10days, by a hand that wore a scented glove (almond or lemon). At 47days of age, females were ovariectomized (OVX), hormone-primed (EB+P), and tested for sexual partner preference with two scented stud males (one almond and one lemon). In each group, females displayed a sexual preference toward males bearing the odor paired with tickling, as observed with longer visits, more solicitations, hops & darts, and receiving more intromissions and ejaculations from the preferred male. In Experiment 2, we used 3-month old, OVX, hormone-primed rats conditioned every 4days for 10 trials. In contrast to juvenile females, adult females failed to prefer males that bore the odor paired with tickling but instead preferred the novel male. These results suggest that tickling has opposite age-dependent effects in the conditioning of partner preference. Tickling in juvenile females appears to act as a rewarding UCS, whereas in adult females it may act as an aversive UCS. Further research is needed to understand brain mechanisms that might account for such differences.

Altered object-in-place recognition memory, prepulse inhibition, and locomotor activity in the offspring of rats exposed to a viral mimetic during pregnancy

Infection during pregnancy (i.e., prenatal infection) increases the risk of psychiatric illnesses such as schizophrenia and autism in the adult offspring. The present experiments examined the effects of prenatal immune challenge on behavior in three paradigms relevant to these disorders: prepulse inhibition (PPI) of the acoustic startle response, locomotor responses to an unfamiliar environment and the N-methyl- d-aspartate antagonist MK-801, and three forms of recognition memory. Pregnant Long–Evans rats were exposed to the viral mimetic polyinosinic-polycytidylic acid (PolyI:C; 4 mg/kg, i.v.) on gestational day 15. Offspring were tested for PPI and locomotor activity before puberty (postnatal days (PNDs)35 and 36) and during young adulthood (PNDs 56 and 57). Four prepulse-pulse intervals (30, 50, 80, and 140 ms) were employed in the PPI test. Recognition memory testing was performed using three different spontaneous novelty recognition tests (object, object location, and object-in-place recognition) after PND 60. Regardless of sex, offspring of PolyI:C-treated dams showed disrupted PPI at 50-, 80-, and 140-ms prepulse-pulse intervals. In the prepubescent rats, we observed prepulse facilitation for the 30-ms prepulse-pulse interval trials that was selectively retained in the adult PolyI:C-treated offspring. Locomotor responses to MK-801 were significantly reduced before puberty, whereas responses to an unfamiliar environment were increased in young adulthood. Both male and female PolyI:C-treated offspring showed intact object and object location recognition memory, whereas male PolyI:C-treated offspring displayed significantly impaired object-in-place recognition memory. Females were unable to perform the object-in-place test. The present results demonstrate that prenatal immune challenge during mid/late gestation disrupts PPI and locomotor behavior. In addition, the selective impairment of object-in-place recognition memory suggests tasks that depend on prefrontal cortex may be particularly vulnerable following prenatal immune challenge.

Juvenile play conditions sexual partner preference in adult female rats

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.

Effects of early life trauma are dependent on genetic predisposition: a rat study

BackgroundTrauma experienced early in life increases the risk of developing a number of psychological and/or behavioural disorders. It is unclear, however, how genetic predisposition to a behavioural disorder, such as attention-deficit/hyperactivity disorder (ADHD), modifies the long-term effects of early life trauma. There is substantial evidence from family and twin studies for susceptibility to ADHD being inherited, implying a strong genetic component to the disorder. In the present study we used an inbred animal model of ADHD, the spontaneously hypertensive rat (SHR), to investigate the long-term consequences of early life trauma on emotional behaviour in individuals predisposed to developing ADHD-like behaviour.MethodsWe applied a rodent model of early life trauma, maternal separation, to SHR and Wistar-Kyoto rats (WKY), the normotensive control strain from which SHR were originally derived. The effects of maternal separation (removal of pups from dam for 3 h/day during the first 2 weeks of life) on anxiety-like behaviour (elevated-plus maze) and depressive-like behaviour (forced swim test) were assessed in prepubescent rats (postnatal day 28 and 31). Basal levels of plasma corticosterone were measured using radioimmunoassay.ResultsThe effect of maternal separation on SHR and WKY differed in a number of behavioural measures. Similar to its reported effect in other rat strains, maternal separation increased the anxiety-like behaviour of WKY (decreased open arm entries) but not SHR. Maternal separation increased the activity of SHR in the novel environment of the elevated plus-maze, while it decreased that of WKY. Overall, SHR showed a more active response in the elevated plus-maze and forced swim test than WKY, regardless of treatment, and were also found to have higher basal plasma corticosterone compared to WKY. Maternal separation increased basal levels of plasma corticosterone in SHR females only, possibly through adaptive mechanisms involved in maintaining their active response in behavioural tests. Basal plasma corticosterone was found to correlate positively with an active response to a novel environment and inescapable stress across all rats.ConclusionSHR are resilient to the anxiogenic effects of maternal separation, and develop a non-anxious, active response to a novel environment following chronic mild stress during the early stages of development. Our findings highlight the importance of genetic predisposition in determining the outcome of early life adversity. SHR may provide a model of early life trauma leading to the development of hyperactivity rather than anxiety and depression. Basal levels of corticosterone correlate with the behavioural response to early life trauma, and may therefore provide a useful marker for susceptibility to a certain behavioural temperament.