Young Adult Female Rats Research Articles

Hypothalamic Insulin-Like Growth Factor-I Receptors Are Necessary for Hormone-Dependent Luteinizing Hormone Surges: Implications for Female Reproductive Aging

Brain IGF-I receptors are required for maintenance of estrous cycles in young adult female rats. Circulating and hypothalamic IGF-I levels decrease with aging, suggesting a role for IGF-I in the onset of reproductive senescence. Therefore, the present study investigated potential mechanisms of action of brain IGF-I receptors in the regulation of LH surges in young adult and middle-aged rats. We continuously infused IGF-I, the selective IGF-I receptor antagonist JB-1, or vehicle into the third ventricle of ovariectomized young adult and middle-aged female rats primed with estradiol and progesterone. Pharmacological blockade of IGF-I receptors attenuated and delayed the LH surge in young adult rats, reminiscent of the LH surge pattern that heralds the onset of reproductive senescence in middle-aged female rats. Infusion of IGF-I alone had no effect on the LH surge but reversed JB-1 attenuation of the surge in young females. In middle-aged rats, infusion of low doses of IGF-I partially restored LH surge amplitude, and infusion of JB-1 completely obliterated the surge. Intraventricular infusion of IGF-I or JB-1 did not modify pituitary sensitivity to exogenous GnRH or GnRH peptide content in the anterior or mediobasal hypothalamus in either young or middle-aged rats. These findings support the hypothesis that brain IGF-I receptor signaling is necessary for GnRH neuron activation under estrogen-positive feedback conditions and that decreased brain IGF-I signaling in middle-aged females contributes, in part, to LH surge dysfunction by disrupting estradiol-sensitive processes that affect GnRH neuron activation and/or GnRH release.

Different expression of α and β mitochondrial estrogen receptors in the aging rat brain: Interaction with respiratory complex V

Recent evidence suggests that hormonal effects on mitochondria could be mediated by mitochondrial estrogen receptors (mtERs). These receptors are new candidates for the beneficial estrogenic effects on mitochondria in different physiological conditions. The aim of this investigation was to study mtER expression during brain aging. We analyzed mtERα and mtERβ expression in cortical, hippocampal and hypothalamic mitochondria of young adult (3months) and aged (18months) female Wistar rats by Western blot. In addition, we explored the interaction of mtERβ with respiratory complex V by using coimmunoprecipitation assays. The results show that mtERα and mtERβ are present in young and aged brain mitochondria. We also demonstrate that mtERs are expressed as variants and have a brain region specific distribution. The predominant mtER variants detected were of 61 and 55KDa for mtERα and of 63 and 52KDa for mtERβ. However, we did not observe differences in the mtERα or β content between the two age groups studied. Additionally, we show that mtERβ interacts with complex V.The overall results demonstrate that there is a differential expression of mtERα and mtERβ variants in different brain areas, indicating that they may participate in different functions in the brain during aging.

Motherhood alters the cellular response to estrogens in the hippocampus later in life

Although controversial, estrogen replacement therapy has been implicated as a possible therapeutic agent for ameliorating age-related cognitive decline in postmenopausal women. We have shown previously that different types of estrogen promote hippocampal neurogenesis in a dose-dependent manner in young adult female rats. However, previous studies have not found a beneficial effect of 17β-estradiol in middle-aged female rats. The aim of the present study was to determine the acute effects of 17β-estradiol, 17α-estradiol, and estrone on hippocampal cell proliferation in middle-aged ovariectomized female rats and to determine whether effects are dependent on previous reproductive experience. Middle-aged multiparous female rats or age-matched virgin female rats were injected subcutaneously with vehicle or 10 μg dose of 17β-estradiol, 17α-estradiol, or estrone, and then given BrdU 30 min later and perfused 24h later to assess cell proliferation. All estrogens significantly upregulated cell proliferation in the hippocampus in middle-aged multiparous females but none of the estrogens upregulated cell proliferation in the middle-aged virgins. Therefore, previous reproductive experience may make the older brain more responsive to estrogens later in life. We also found that 17α-estradiol upregulated cell proliferation to a greater degree than the other estrogens in the multiparous females. Together these findings may lead to the development of new therapeutic advances in the treatment of symptoms associated with menopause in women.

Phencyclidine (PCP) produces sexually dimorphic effects on voluntary sucrose consumption and elevated plus maze behavior

Previous research in our laboratory indicates that the psychotomimetic drug phencyclidine (PCP) reduces voluntary sucrose consumption in male rats, potentially modeling the schizophrenic symptom of anhedonia. Given reports from the clinical literature that schizophrenia has a later age of onset and more favorable outcome in females, PCP might be expected to have sexually dimorphic effects in animal models of schizophrenia such as PCP-induced decreases in voluntary sucrose consumption. Young adult (66 days old) and adult (109 days old) male and female rats were trained to drink sucrose during a 30 min/day presentation protocol. On the day prior to the test day, animals were treated with PCP (15 mg/kg) or saline four hours after the onset of the sucrose presentation (20 h prior to the sucrose on the test day). PCP decreased sucrose consumption on the test day similarly in adult males and females, although females also showed decreased water consumption. In young animals, PCP decreased sucrose consumption in males but not in females. These results are consistent with the prediction that females will be less sensitive to the schizophrenia-like behavioral effects of PCP. In a separate study, the same animals were tested in an elevated plus maze one to two months after testing for voluntary sucrose consumption. Significant sex × drug interaction effects on a number of measures in the elevated plus maze indicated that prior exposure to PCP had an anxiolytic effect in females and an anxiogenic effect in males. While unexpected, this finding indicates an additional sexually dimorphic effect of PCP on behavior and its potential relevance to the PCP model of schizophrenia is discussed.

Is Progesterone Worth Consideration as a Treatment for Brain Injury?

male laboratory rats and mice can cross the blood–brain barrier [10] and reduce edema levels after TBI [11, 12]; reduce lipid per-oxidation and isoprostanes, which, in turn, contribute to postinjury ischemic condi-tions [13]; generate metabolites that reduce proapoptotic and increase antiapoptotic en-zymes [14] and the expression of proinflam-matory genes and their protein products [3, 15]; influence the expression of aquaporins implicated in the resolution of edema [16]; in different models of cerebral ischemia, signif-icantly reduce the area of necrotic cell death and improve behavioral outcomes [17]; pro-tect neurons distal to the injury that would normally die [4, 18]; enhance oligodendro-cyte-induced remyelination in young and old rats with demyelinating disorders [19, 20]; and produce significant sparing of cognitive, sensory, and spatial learning performance after bilateral medial frontal cortex injury [18]. Progesterone has been shown to have beneficial effects in 22 different injury mod-els; a number of extensive reviews discuss these data [21–23].To date, most research on progesterone and its metabolites has focused on the treat-ment of TBI [3–5, 7, 13, 24–26]. This line of research originated when researchers in our laboratory found that, after bilateral con-tusion injury to the medial frontal cortex in young adult male and female rats, 5 days of treatment with progesterone significantly improved spatial learning and sensory per-formance, compared with controls given in-jections of the vehicle alone.The first successful clinical trial for the treatment of TBI in more than 30 years of research was recently completed. This Na-tional Institute of Neurological Disorders and Stroke (NINDS)–sponsored phase 2a single-center clinical trial for progesterone in the treatment of moderate-to-severe adult TBI [27] found that the mortality rate among

Induction of PTEN-p53 Crosstalk in Mammary Epithelial Cells: A Novel Mechanism of Breast Cancer Prevention by the Dietary Factor Genistein.

Abstract Consumption of soy foods either at an early age or for lifetime has been associated with reduced risk for developing breast cancer in humans and in animal models. However, this association continues to be controversial and the precise mechanisms for protection remain elusive. Among the soy products, the isoflavone genistein (GEN) has been widely suggested to confer mammary tumor protection. Previously we demonstrated the increased expression of tumor suppressors PTEN and p53 in mammary epithelial cells (MECs) isolated from young adult female rats fed dietary soy protein isolate (SPI) or casein (CAS) supplemented with GEN, when compared to MECs from rats fed the control (CAS) diet. Since NMU-administered rats fed SPI had reduced tumor incidence and increased tumor latency than those fed CAS, PTEN and p53 likely mediate the observed tumor resistance with SPI in vivo. We hypothesized that GEN induction of PTEN and p53 in MECs results in the formation of a PTEN/p53 functional complex to negatively regulate breast cancer development. Here, we used the human non-tumorigenic, ER-negative mammary epithelial cell line, MCF-10A, as an in vitro system to mechanistically dissect ER-independent actions of GEN involving PTEN and p53. GEN (40 nM, 2μM) augmented PTEN and p53 expression in treated relative to control cells. GEN also induced nuclear co-localization and physical association of PTEN and p53. To test a functional consequence of GEN-induced PTEN/p53 cross-talk on mammary epithelial phenotype, we analyzed GEN effects on cell cycle progression and acini formation in 3D cultures. Our results showed attenuated cell proliferation and lower cyclin D1 and pleiotrophin transcript levels in GEN-treated cells, which were abrogated by small interfering RNA to PTEN, indicating PTEN-dependence. Using FACS analysis, we showed that GEN induced cell cycle arrest at G0-G1 phase. Treatment with GEN promoted early acini formation of MECs grown in Matrigel, which temporally coincided with PTEN-dependent suppression of p21 and p27 transcript levels. Further analyses of GEN effects on MECs demonstrated induction by GEN of PTEN promoter-luc reporter activity as measured by dual-luciferase assay. Interestingly, treatment with siRNA to either PTEN or p53 reduced basal and GEN-induced PTEN promoter activity. Given that p53 binds to the PTEN promoter, our results suggest a feed-forward cycle in which dietary factor (GEN) induction of nuclear PTEN leads to PTEN promotion of its own signaling. By maintaining a stable pool of nuclear p53 to boost its transcription, PTEN ensures its continuous expression in MECs to favor cell differentiation. These data elucidate a novel mechanism by which dietary factors with PTEN-inducing activity may attenuate breast cancer risk and development. Funding by USDA-CRIS 6251-5100002-06S and the Department of Defense Breast Cancer Program (0810548). Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3149.

Propriedades mecânicas do músculo gastrocnêmio de ratas, imobilizado e posteriormente submetido a diferentes protocolos de alongamento

O alongamento é amplamente utilizado na prática clínica da fisioterapia e no desporto, porém, as alterações mecânicas que essa técnica gera no músculo esquelético são pouco exploradas cientificamente. Este estudo avaliou as alterações mecânicas que acometem o músculo gastrocnêmio de ratas Wistar, adultas jovens, após 14 dias de imobilização e, secundariamente, submetido a alongamento manual passivo por 10 dias consecutivos, aplicado uma ou duas vezes ao dia. Foram utilizados 50 animais, sendo 10 para cada grupo: Controle (GC); Imobilizado (GI); Imobilizado e Liberado (GIL); Imobilizado e alongado uma vez ao dia (GIA1); e Imobilizado e alongado duas vezes ao dia (GIA2). O músculo gastrocnêmio foi submetido ao ensaio mecânico de tração, onde foram avaliadas as propriedades de carga e alongamento nos limites máximo e proporcional, além de rigidez e resiliência. A imobilização reduziu os valores das propriedades mecânicas de carga no limite máximo (CLM), carga no limite proporcional (CLP), alongamento no limite máximo (ALM), rigidez e resiliência, em 44,4%, 34,4%, 27,6%, 64,4% e 54%, respectivamente, quando comparados com os valores do GC. A remobilização livre e o alongamento restauraram as propriedades de CLM, CLP, ALM, rigidez e resiliência do músculo, exceto para o GIA2, que foi incapaz de restabelecer a propriedade de ALM (31,3% menor que GC). Concluí-se, portanto que, após 14 dias de imobilização segmentar, cargas individuais de alongamento e a livre movimentação permitem restituir as propriedades mecânicas do tecido muscular.

Chronic treatment with polychlorinated biphenyls (PCB) during pregnancy and lactation in the rat: Part 2: Effects on reproductive parameters, on sex behavior, on memory retention and on hypothalamic expression of aromatase and 5alpha-reductases in the offspring

The gender-specific expression pattern of aromatase and 5alpha-reductases (5alpha-R) during brain development provides neurons the right amount of estradiol and DHT to induce a dimorphic organization of the structure. Polychlorinated biphenyls (PCBs) are endocrine disruptive pollutants; exposure to PCBs through placental transfer and breast-feeding may adversely affect the organizational action of sex steroid, resulting in long-term alteration of reproductive neuroendocrinology. The study was aimed at: a) evaluating the hypothalamic expression of aromatase, 5alpha-R1 and 5alpha-R2 in fetuses (GD20), infant (PN12), weaning (PN21) and young adult (PN60) male and female rats exposed to PCBs during development; b) correlating these parameters with the time of testicular descent, puberty onset, estrous cyclicity and copulatory behavior; c) evaluating possible alterations of some non reproductive behaviors (locomotion, learning and memory, depression/anxiety behavior). A reconstituted mixture of four indicator congeners (PCB 126, 138, 153 and 180) was injected subcutaneously to dams at the dose of 10 mg/kg daily from GD15 to GD19 and then twice a week till weanling. The results indicated that developmental PCB exposure produced important changes in the dimorphic hypothalamic expression of both aromatase and the 5alpha-Rs, which were still evident in adult animals. We observed that female puberty onset occurs earlier than in control animals without cycle irregularity, while testicular descent in males was delayed. A slight but significant impairment of sexual behavior and an important alteration in memory retention were also noted specifically in males. We conclude that PCBs might affect the dimorphic neuroendocrine control of reproductive system and of other neurobiological processes.

Early maternal separation increases symptoms of activity-based anorexia in male and female rats.

Running activates the hypothalamic-pituitary-adrenal (HPA) axis, increasing the release of stress hormones known to exert anorexic effects. HPA axis reactivity is strongly influenced by early postnatal manipulations, including removal of pups from the dam for short (handling) or prolonged (maternal separation) durations during the preweaning period. The authors examined the effects of handling and maternal separation on food intake, body weight loss, and running rates of young adult male and female rats in the activity-based anorexia (ABA) paradigm. Postnatal treatment did not affect adaptation to a 1-hr restricted feeding schedule before the introduction of wheel running. During the ABA paradigm, maternally separated animals lost weight faster, ate less, ran more, and required fewer days to reach removal criterion compared with handled rats. Females were particularly vulnerable. These findings indicate that early postnatal treatment and sex influence ABA.

Regional variability in age-related loss of neurons from the primary visual cortex and medial prefrontal cortex of male and female rats

During aging, changes in the structure of the cerebral cortex of the rat have been seen, but potential changes in neuron number remain largely unexplored. In the present study, stereological methods were used to examine neuron number in the medial prefrontal cortex and primary visual cortex of young adult (85–90 days of age) and aged (19–22 months old) male and female rats in order to investigate any age-related losses. Possible sex differences in aging were also examined since sexually dimorphic patterns of aging have been seen in other measures. An age-related loss of neurons (18–20%), which was mirrored in volume losses, was found to occur in the primary visual cortex in both sexes in all layers except IV. Males, but not females, also lost neurons (15%) from layer V/VI of the ventral medial prefrontal cortex and showed an overall decrease in volume of this region. In contrast, dorsal medial prefrontal cortex showed no age-related changes. The effects of aging clearly differ among regions of the rat brain and to some degree, between the sexes.

T01-O-16 Restoration of female genital vasocongestive arousal responses in young and aged rats

Objectives To examine whether the actions of nitric oxide (NO) were critical to the apomorphine-generated genital vasocongestive arousal (GVA) responses in both intact and ovariectomized (OVX) young adult female rats. We also investigated whether the diminished GVA responses in aged rats could be restored using an antihypertensive treatment. Design and Methods In female Wistar rats (n=8), apomorphine- induced GVA responses were assessed following various treatments. Young adult females were ovariectomized or treated with the NO synthase (NOS) inhibitor Nnitro-L-arginine methyl ester (30mg/kg, i.v.) followed by an NO-mimetic, sodium nitroprusside (10mg/kg/min, i.v.). Aged females (18 months-old; n=8) were treated for 2 weeks with the angiotensin converting enzyme inhibitor (ACEI) enalapril (30mg/kg per day, p.o.) + low sodium (0.04%). Results Age-associated reduction in sexual responses in normotensive rats was greatly enhanced by brief, aggressive antihypertensive treatment. The enhanced vasocongestive responses persisted for 5 weeks off-treatment. Both OVX and NOS inhibition significantly decreased sexual responses in the young female rats. Systemic administration of an NO-mimetic recovered vasocongestive responses in the NOS blocked rats, but not in OVX animals. Conclusions Brief aggressive ACEI treatment markedly improved sexual responses in aged female rats, and systemic delivery of a NO-mimetic recovered sexual responses in globally NOS blocked animals.

Restoration of Female Genital Vasocongestive Arousal Responses in Young and Aged Rats

Treatments of aged, male hypertensive rats that induce vascular remodeling or that normalize endothelial function are known to produce sustained improvements in erectile function. Whether the treatments targeting these processes benefit female genital vasocongestive arousal (GVA) responses is currently not known. To determine whether the actions of nitric oxide (NO) are critical to the apomorphine (APO)-generated GVA responses in both intact and ovariectomized OVX young adult female rats (before any aging-associated decreases in the responses). In addition, we also investigated whether the diminished GVA responses in aged rats could be restored, at least in part, using an antihypertensive treatment, which is known to enhance erectile responses and improve general vascular function in male rats. In female Wistar rats, APO-induced GVA responses (80 microg/kg, subcutaneously [sc], 30 minutes) were assessed by videomonitoring following various treatments. Young adult females were ovariectomized or were treated with the nitric oxide synthase (NOS) inhibitor N-nitro-L-arginine methyl ester (30 mg/kg, iv), followed by an NO mimetic, sodium nitroprusside (10 microg/kg/minute, intravenous). Aged females (18 months) were treated for 2 weeks with the angiotensin converting enzyme (ACE) inhibitor, enalapril (30 mg/kg/day, orally) plus low sodium (0.04%). APO-induced GVA responses in female rats. There was an age-associated reduction in sexual responses in normotensive rats that was greatly enhanced (fourfold) by brief, aggressive antihypertensive treatment. The enhanced vasocongestive responses persisted for a 5-week off-treatment. Both OVX and NOS inhibition significantly decreased sexual responses by approximately 80% in young female rats. Systemic administration of an NO mimetic recovered vasocongestive responses in the NOS-blocked rats, but not in OVX animals. Although mechanisms were not established, the major findings were that brief aggressive ACE inhibitor treatment markedly improved sexual responses in aged female rats, and systemic delivery of an NO mimetic recovered sexual responses in globally NOS-blocked animals.

Effects of estrogen receptor agonists on regulation of the inflammatory response in astrocytes from young adult and middle-aged female rats

Estrogen has been shown to attenuate the inflammatory response following injury or lipopolysaccharide treatment in several organ systems. Estrogen's actions are transduced through two estrogen receptor sub-types, estrogen receptor (ER) -alpha and estrogen receptor-beta, whose actions may be overlapping or independent of each other. The present study examined the effects of ERα- and ERβ-specific ligands in regulating the inflammatory response in primary astrocyte cultures. Pre-treatment with 17β-estradiol (ERα/ERβ agonist), HPTE (ERα agonist/ERβ antagonist) and DPN (ERβ agonist) led to attenuation of IL-1β, TNFα, and MMP-9 in astrocyte media derived from young adult (3-4 mos.) and reproductive senescent female (9-11 mos., acyclic) astrocyte cultures, while pretreatment with PPT (ERα agonist) attenuated IL-1β (but not MMP-9) in both young and senescent-derived astrocyte cultures. Our previous work determined that 17β-estradiol was unable to attenuate the LPS-induced increase in IL-1β in olfactory bulb primary microglial cultures derived from either young adult or reproductive senescent females. In young adult-derived microglial cultures, the LPS-induced increase in IL-1β was not attenuated by pre-treatment with 17β-estradiol, PPT or HPTE. Interestingly, the ERβ agonist, DPN significantly decreased IL-1β following LPS treatment in young adult-derived microglia. Thus while both microglia and astrocytes synthesize and release inflammatory mediators, the present data shows that compounds which bind ERβ are more effective in attenuating proinflammatory cytokines in both cell types and may therefore be a more effective agent for future therapeutic use.

Toxicity Profile of Lutein and Lutein Ester Isolated From Marigold Flowers (Tagetes erecta)

Lutein is a carotenoid with antioxidant properties and is commonly present in many fruits, vegetables, and egg yolk. Lutein affords protection against the development of the two common eye diseases of aging: cataract and macular degeneration. As the dietary lutein concentration is much lower compared to the actual requirement to reduce macular degeneration, supplementation of lutein is under consideration. There are very few data on the toxicity of lutein. In the present study, the authors have evaluated the short-term and long-term toxicity profile of lutein and its esterified form isolated from marigold flowers (Tagetes erecta) in young adult male and female Wistar rats. Lutein and its ester form administered orally at doses of 4, 40, and 400 mg/kg body weight for 4 weeks for short-term toxicity study and 13 weeks for a subchronic toxicity study did not produced any mortality, change in body weight, food consumption pattern, organ weight, and other adverse side reactions. Administration of lutein and ester form did not alter the hepatic and renal function, and did not produce any change in the hematological parameters and in lipid profile. Histopathological analysis of the organs supported the nontoxicity of lutein and its ester form.

Prenatal exposure to cocaine is associated with increased number of spine synapses in rat prelimbic cortex

Prenatal exposure to cocaine has been associated with cognitive deficits in children and in animal models. An excess activation of pyramidal neurons in the prefrontal cortex has been proposed as a potential cause for these deficits based on previous studies. The goal of this study was to determine if prenatal exposure to cocaine was associated with an increase in the number of excitatory synapses on dendritic spines in layer II/III of the prelimbic cortex. Frontal cortex of young adult male and female rats, exposed to either saline or cocaine (3 mg/kg i.e., twice a day, embryonic day 10-20), were examined using electron microscopy and the number of asymmetric spines synapses were estimated using the physical disector method. Both male and female rats prenatally exposed to cocaine had about twice as many synapses on dendritic spines as the prenatal saline controls. The increase in number of excitatory synaptic inputs associated with prenatal cocaine exposure could contribute to the increased neuronal activation and cognitive deficits noted.

Quantification and regulation of the subcellular distribution of bile acid coenzyme A:amino acid N-acyltransferase activity in rat liver

Bile acid coenzyme A:amino acid N-acyltransferase (BAT) is responsible for the amidation of bile acids with the amino acids glycine and taurine. To quantify total BAT activity in liver subcellular organelles, livers from young adult male and female Sprague-Dawley rats were fractionated into multiple subcellular compartments. In male and female rats, 65-75% of total liver BAT activity was found in the cytosol, 15-17% was found in the peroxisomes, and 5-10% was found in the heavy mitochondrial fraction. After clofibrate treatment, male rats displayed an increase in peroxisomal BAT specific activity and a decrease in cytosolic BAT specific activity, whereas females showed an opposite response. However, there was no overall change in BAT specific activity in whole liver homogenate. Treatment with rosiglitazone or cholestyramine had no effect on BAT activity in any subcellular compartment. These experiments indicate that the majority of BAT activity in the rat liver resides in the cytosol. Approximately 15% of BAT activity is present in the peroxisomal matrix. These data support the novel finding that clofibrate treatment does not directly regulate BAT activity but does alter the subcellular localization of BAT.

Foster mother care but not prenatal morphine exposure enhances cocaine self‐administration in young adult male and female rats

The present study was designed to investigate cocaine self-administration in adult male and female rats exposed prenatally to morphine. Pregnant dams were injected two times a day with either saline, analgesic doses of morphine or no drug at all (controls) on gestation Days 11-18. One day after birth, litters were cross-fostered such that control dams were paired with one another and their litters were crossed; saline- and morphine-treated dams were paired and half of each saline litter was crossed with half of each morphine litter. Thus, each mother (control, saline, and morphine) raised half of her own and half of the adopted litter. At the age of 60 days, males and females were trained first to lever press for sucrose pellets and then for cocaine. Once the lever-pressing behavior was learned and baseline level of this activity was established, animals received a cocaine (.5 mg/kg per infusion) reward for each correct response on the active lever during the next 9-day session. The data demonstrate that adult control, saline- and morphine-exposed male rats self-administer cocaine at a similar rate independent of their prenatal treatment. Adult female rats self-administer cocaine at a higher rate than male rats. Further, saline- and morphine-exposed females in diestrus self-administer more than females in proestrus phase of the estrous cycle, while control females show no such differences. In addition, fostering induces increase in cocaine self-administration in all groups of male rats regardless of prenatal drug exposure. In females, the only fostering-induced increase is in prenatally saline-exposed female rats raised by morphine-treated foster mother. Thus, our results suggest that the prenatal drug exposure does not induce changes in lever-pressing behavior for cocaine reward in adult male and female rats, but it sensitizes the animals to postnatal stimuli such as gonadal hormones and/or rearing conditions that result in increased drug self-administration.

Age-related dendritic hypertrophy and sexual dimorphism in rat basolateral amygdala

Little research has examined the influence of aging or sex on anatomical measures in the basolateral amygdala. We quantified spine density and dendritic material in Golgi–Cox stained tissue of the basolateral nucleus in young adult (3–5 months) and aged (20–24 months) male and female Long-Evans rats. Dendritic branching and spine density were measured in principal neurons. Age, but not sex, influenced the dendritic tree, with aged animals displaying significantly more dendritic material. Previous findings from our laboratory in the same set of subjects indicate an opposite effect of aging on dendritic material in the medial prefrontal cortex and hippocampus. We also report here a sex difference across ages in dendritic spine density, favoring males.

EFFECTS OF CHRONIC PRENATAL STRESS ON ADULT BODY WEIGHT, PERCENT BODY FAT WEIGHT AND PLASMA LEPTIN IN MALE RATS

Chronic stress experienced by the mother during pregnancy increases potential disease states in the offspring, such as type-2 diabetes and obesity (Mueller, 2006) possibly due to ‘programming’ of the fetus. Rat pups conceived, gestated and born during exposure to chronic stress induced by continuous 20 rpm centrifugation were characterized by low birth weight, adult overweight, and increased adult body fat. Young adult male and female rats were adapted to centrifugation for one week prior to mating. Centrifugation was discontinued at parturition. Centrifuged (CF) and non-centrifuged (nCF) control neonates were fostered to non-manipulated, newly parturient dams. As compared nCF male pups, birth weights of CF male pups were significantly lower (Mean s.e.: nCF, 7.49±0.22gm, CF, 6.30±0.11gm; p<0.01). Body weights remained significantly (p<0.05) lower until Postnatal day (P)12. At P90, body weights of CF males were significantly greater those of nCF males (Mean s.e.: nCF, 487±7 gm; CF, 519±11 gm; p<0.02). Using the Total Body Electrical Conductivity (TOBEC) to determine live body composition, total body fat weight was significantly higher in CF than nCF males (Mean % s.e.: nCF, 44±0.32; CF, 45±0.47; p<0.03). In addition, the appetite hormone, leptin, was significantly (p<0.05) elevated in CF relative to nCF males. Our data suggest that chronic prenatal stress alters the intrauterine milieu, thereby programming adult overweight with correlated changes in body fat and leptin. (NIH Grant HD50201; NASA Grant NNA04CK83).

Estrogen modulates learning in female rats by acting directly at distinct memory systems

Physiologically high levels of circulating estradiol enhance the use of place learning and impair the use of response learning to find food on a land maze. These two types of learning are impaired by lesions of distinct neuronal structures, i.e. the hippocampus and striatum, respectively. Moreover, it has been shown in male rats that compromising hippocampal function can promote the use of response learning, while compromising striatal function can promote place learning. These findings suggest an ongoing competition between the hippocampus and striatum during cognition, such that intact functioning of one structure somehow obstructs the relative participation of the other. The goal of this study was to determine if estrogen’s opposing effects on place and response learning in female rats are due to direct actions, either independent or interacting, at the hippocampus and striatum. We infused 0.5 μM 17β-estradiol 3-sulfate sodium or vehicle bilaterally into the dorsal hippocampus or dorsolateral striatum of ovariectomized young adult female rats, 48, 24 and 2 h before training. Rats were tested on one of three appetitive tasks in a Y-maze: place learning, response learning, or response learning with reduced visual cues (cue-poor condition). Intrahippocampal estradiol infusions enhanced place learning, reversing a cannula-induced impairment, whereas intrastriatal infusions had no effects on place learning. Estradiol infusions into neither structure significantly affected response learning when extramaze cues were visible. However, in the response task, cue-poor condition, intrastriatal but not intrahippocampal infusions impaired learning. These data demonstrate that estrogen modulates place and response learning at the hippocampus and striatum respectively, most likely through independent actions at these two structures.