Posttraining estradiol injections enhance memory in ovariectomized rats: cholinergic blockade and synergism

Three models (independent, interdependent, and mediational) were hypothesized in this study, to examine the interrelation of personality, family, and peer determinants and their effects on tobacco use by young adults. Mothers were first interviewed about their children when they were between the ages of 1 and 10 years old. Three subsequent interviews were conducted with the children when they reached adolescence and young adulthood. Results show support for the mediational model. In accordance with family interactional framework conceptions, there was a sequence in patterning: from parenting during early adolescence; to personality and peer factors, extending to smoking in late adolescence; and culminating in smoking in adulthood. With a developmental approach, a number of psychosocial measures were related in both younger and older children. Nevertheless, some interesting developmental differences emerged. The findings suggest at least four possible targets for therapeutic or preventive intervention: the parent, the child, the adolescent, and the peer group.     

Prevention of bone loss by percutaneous estradiol implants in ovariectomized rats

This study was conducted to investigate whether hydroxyapatite (HAP) is appropriate as a percutaneous drug carrier for estradiol (E2) for the suppression of bone loss. Ten-week-old female Sprague-Dawley rats were subjected either to bilateral ovariectomy (OVX) or to sham surgery (control). Ovariectomized rats were implanted percutaneously with E2-HAP disks containing low, medium or high doses of estradiol (50, 250, or 500 micrograms E2/rat, respectively). Ovariectomized rats without implant and OVX rats implanted only with HAP served as additional controls. All rats were sacrificed 90 days after surgery. At the end of the experiment, bone mineral density of the lumbar spine was measured by dual energy X-ray absorption, and serum E2 was assayed by radioimmunoassay. The bone mineral density of OVX and HAP-treated OVX rats decreased by 18% compared to sham surgery rats, but decreased by only 13, 7, and 3% in rats treated with 50, 250, and 500 micrograms E2/rat, respectively. The in vitro release of E2 from E2-HAP devices was determined by an HPLC method. Estradiol release from the HAP devices followed almost a zero-order kinetics. Estradiol remained intact in E2-HAP implants for up to six months when stored at 5, 25, and 40 degrees C. This study indicates that E2-HAP implants are effective in suppressing bone loss in the spine of OVX rats in a dose-dependent manner.     

Adolescent cocaine residually impairs working memory and enhances fear memory in rats.

The residual effects of cocaine during adolescence on memory in male young adult rats were studied. Animals were injected with 20 mg/kg cocaine on postnatal Days 28 through 35, whereas lab-chow (LC) and pair-fed (PF) control subjects received saline. Assessment of spatial working and long-term memory in the Morris water maze, and 72-h retention of an inhibitory avoidance task was conducted at about 5 and 9 weeks postcocaine, respectively. Relative to PF control subjects, cocaine-treated subjects showed impairments in the water maze when required to swim to the hidden platform placed in a quadrant diagonal from the location of its original location (i.e., on reversal learning). These same drug-treated animals, however, exhibited enhanced inhibitory avoidance retention relative to both control groups. These seemingly disparate findings are seen as being consistent with previous data showing that cocaine during adolescence residually impairs spatial memory and leads to enhanced fear responses. Moreover, when taken with previous findings from our laboratory, the present water maze data indicate that the deleterious effects of cocaine, when administered during adolescence, is delayed until 5 weeks after initiation of abstinence. It is speculated that alterations to limbic circuitry, especially those associated with the amygdala, account for the behavioral results observed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Influence of aging on cortical and trabecular bone response to estradiol treatment in ovariectomized rats

Three groups (n = 15/group) of 6-, 12- and 30-month-old (mature, old and senescent animals, respectively) female Wistar rats on a diet (6 g/100 g BW/ day) containing 0.8% calcium and 0.8% inorganic phosphorus were studied. Within each group, 10 rats were ovariectomized surgically and 5 injected s.c. with 17 beta-estradiol (E rats, 10 micrograms/kg BW/48 h) and 5 with solvent alone (OVX rats) from day 2 until day 60 after ovariectomy. Five other rats were sham-operated (SH rats) and received solvent only. All rats were killed by exsanguination 60 days after ovariectomy. Neither ovariectomy nor estradiol treatment had a significant effect upon tibial mechanical properties in 6-, 12- and 30-month-old animals. Bone mineral density (BMD) and bone mineral content (BMC) of the distal femur and BMC of the whole femur were decreased by ovariectomy in 6- and 12-month-old rats, but were not different in the SH and E groups. In senescent animals, in which the lowest BMD and BMC were measured, estradiol treatment was more effective in increasing these parameters than in adult and old rats. Image analysis of the distal femoral diaphysis showed that estradiol treatment prevented trabecular bone loss induced by senescence and/or ovariectomy. In each group, urinary deoxypyridinoline excretion and plasma osteocalcin concentration were higher in the OVX animals than in the controls, consistent with increased bone turnover in the estrogen-deficient state. Both biochemical turnover markers were reduced in the estrogen-treated groups. These results indicate that 17 beta-estradiol is particularly effective at preventing high-turnover-induced osteopenia in 30-month-old animals.     

Inhibition of prolactin secretion delays extinction of circadian LH surges in ovariectomized rats bearing estradiol implants

Ovariectomized rats bearing Silastic capsules containing estradiol exhibit a daily afternoon surge of luteinizing hormone (LH) which decreases with time until it is undetectable by Day 10 after implantation of estradiol. Increases in basal prolactin levels as well as afternoon surges are also observed. To determine if increased prolactin secretion contributed to the extinction of the circadian LH surges, we examined the patterns of LH and prolactin secretion in rats in which prolactin was suppressed by bromocriptine treatment. In vehicle-treated control rats, the magnitude of the LH surges decreased with time. Large LH surges were observed on Days 2 and 4. A significant decrease in the surge occurred on Day 6, and it disappeared by Day 10. Animals treated with bromocriptine also exhibited large LH surges on Days 2 and 4, and in addition, secreted a greater amount of LH than the control group on Days 6, 8, and 10. In ovariectomized rats bearing estradiol implants, large afternoon surges in prolactin were observed and by Day 6, basal prolactin levels were also elevated. Bromocriptine treatment completely suppressed prolactin secretion through Day 6, but a small afternoon rise was observed on Days 8 and 10. These findings suggest that elevated prolactin secretion may be one factor contributing to the extinction of circadian LH surges in the estrogen-treated rat.     

17-β estradiol administration attenuates deficits in sustained and divided attention in young ovariectomized rats and aged acyclic female rats.

Recent evidence suggests that estrogen may interact with the basal forebrain cholinergic system to influence learning. The authors examined whether the loss of estrogen following ovariectomy (Experiment 1) or the disruption to the estrogen cycle during aging (Experiment 2) impaired performance of the 5-choice serial reaction time task (5-CSRT)--a sustained and divided attention task sensitive to cholinergic challenges in rats. In Experiment 1, posttraining ovariectomy in young rats did not disrupt baseline performance but did impair performance when attention was challenged by variation in the intertrial interval (ITI) or in the intermittent presentation of a novel distracting auditory stimulus. Administration of 17-β estradiol rescued these impairments. Through the use of a within-subjects design, Experiment 2 revealed that 17-β estradiol did not influence the baseline performance of 21-month-old female rats trained on the 5-CSRT task from a young age but did improve performance when attention was challenged by varying the ITI or by presenting a distracting auditory cue. The results indicate that 17-β estradiol administration can improve specific components of attention in young ovariectomized rats and gonadally intact aged female rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The metabolic fate of [3H]estradiol in relation to dietary intake of boron in ovariectomized rats

It has been reported that boron (B) deprivation reversibly lowers plasma estradiol levels in postmenopausal women. In order to establish whether this reflects disturbances in the estrogen catabolic pathway and in particular in catechol estrogen metabolism, the influence of dietary B on the catabolism of [3H]estradiol-17 beta has been studied in ovariectomized rats. Rats were given diets containing < 0.1 or 40 mg B.kg-1, ovariectomized and then infused with [3H]estradiol-17 beta using osmotic pumps. Analysis of urine samples for conjugated, catechol and non-catechol estrogens did not reveal any effects of B on the recovery or the metabolic fate of tritium from the infused estradiol. These results do not therefore support the proposal that B influences estrogen catabolism by interacting with catechol estrogens.     

Posttraining intrahippocampal estradiol injections enhance spatial memory in male rats: interaction with cholinergic systems

Male Long-Evans rats received an 8-trial training session in a spatial water maze task, followed by a unilateral posttraining intrahippocampal injection of either estradiol (1.0 microgram/0.5 microliter) or saline. Retention was tested 24 hr later, and latency to escape was used as a measure of memory. Retention test escape latencies of rats given intrahippocampal injections of estradiol were lower than those of saline-treated rats, indicating an enhancement of memory. Intrahippocampal injections of estradiol delayed 2 hr posttraining did not affect retention. In Experiment 2, the memory enhancing effect of intrahippocampal injection of estradiol was blocked by peripheral administration of a subeffective dose (0.1 mg/kg) of the cholinergic antagonist scopolamine. Intrahippocampal injections of estradiol enhance memory in male rats, and estradiol may influence memory through an interaction with muscarinic cholinergic systems.     

Sleep selectively enhances hippocampus-dependent memory in mice.

Sleep has been implicated as playing a critical role in memory consolidation. Emerging evidence suggests that reactivation of memories during sleep may facilitate the transfer of declarative memories from the hippocampus to the neocortex. Previous rodent studies have utilized sleep-deprivation to examine the role of sleep in memory consolidation. The present study uses a novel, naturalistic paradigm to study the effect of a sleep phase on rodent Pavlovian fear conditioning, a task with both hippocampus-dependent and -independent components (contextual vs. cued memories). Mice were trained 1 hour before their sleep/rest phase or awake/active phase and then tested for contextual and cued fear 12 or 24 hr later. The authors found that hippocampus-dependent contextual memory was enhanced if tested after a sleep phase within 24 hr of training. This enhancement was specific to context, not cued, memory. These findings provide direct evidence of a role for sleep in enhancing hippocampus-dependent memory consolidation in rodents and detail a novel paradigm for examining sleep-induced memory effects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Genistein-induced changes in lipid metabolism of ovariectomized rats

The effect of the isoflavone, genistein, on the lipid metabolism of ovariectomized rats was studied. Three types of experiments were performed. In the first one, the rats were fed diets supplemented with 0.01 or 0.1% of genistein for 14 days. In the second and third experiments, the direct effect of genistein on the liver and fat tissue were measured respectively by means of liver perfusion or incubation of isolated adipocytes with the isoflavone. Genistein in food significantly decreased blood serum and muscle triglyceride concentrations and increased the level of free fatty acids in serum. Serum free cholesterol was diminished and liver cholesterol was enhanced after genistein ingestion. When genistein acted directly on the liver during perfusion, a smaller incorporation of 14C-glucose into lipids was observed, and in parallel a greater output of free fatty acids into the medium was noticed. These changes were accompanied by diminution of the liver triglyceride contents. Genistein, acting on the adipocytes strongly depressed both basal and insulin-induced lipid synthesis, when glucose was used as a substrate. The effect of the isoflavone alone on the lipolysis in the adipocytes was negligible. However, it intensified lipolysis induced by epinephrine. The results obtained let us conclude that genistein in food can reduce the fattening processes in ovariectomized rats. This effect of genistein may be attributed, at least in part, to its direct influence on lipid metabolism in the liver and adipose tissue.     

Posttraining norepinephrine infusion into the central amygdala differentially enhances later retention in Roman high-avoidance and low-avoidance rats.

Memory-enhancement effects of norepinephrine (NE) were investigated by infusing NE into the central amygdala (CEA) of Roman high-avoidance (RHA) and low-avoidance (RLA) rats after training on active and passive behaviors in the defensive-burying paradigm. During acquisition, both lines spent comparable time in burying behavior. RLA rats, but not RHA rats, also displayed substantial immobility. During retention, the CSF-treated RLA rats mostly displayed immobility to the nonelectrified probe, whereas the RHA rats showed neither burying nor immobility. In the RLA rats, high-dose (200 ng), but not low-dose (20 ng), NE infusion enhanced the duration of the passive response (immobility) without affecting the active response. NE given into the CEA of RHA rats caused a selective dose-dependent appearance of the active behavioral component. The results suggest a phenotype-dependent effect of intra-amygdaloid NE on memory processes in the rat. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of estradiol benzoate and MER-25 on ethanol consumption in the ovariectomized rat.

Administered daily injections of estradiol benzoate (EB) to ovariectomized Wistar rats given continuous access to a 10% ethanol solution, water, and laboratory chow in 3 experiments with 78 Ss. EB led to decreases in ethanol consumption. The suppression was transient; ethanol consumption returned to the level of oil-treated controls after 14 days despite continued hormone administration. This pattern of change in ethanol consumption closely resembled previously reported effects of EB on food intake. It is proposed that a common mechanism is responsible for EB-induced suppression of both food and ethanol intake. Ethamoxytriphetol, MER-25, which antagonizes many estrogen-dependent effects but which mimics the action of EB on food intake, also led to decreases in ethanol consumption that paralleled those reported for food intake. It is suggested that voluntary consumption of ethanol by the rat is largely due to its caloric content. The relevance of these results for reports of decreased ethanol intake during pregnancy is discussed. (42 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Self-referencing enhances memory specificity with age.

Self-referencing has been identified as an advantageous mnemonic strategy for young and older adults. However, little research has investigated the ways in which self-referencing may influence older adults' memory for details, which is typically impaired with age, beyond memory for the item itself. Experiment 1 assessed the effects of self- and other-referencing on memory for visually detailed pictures of objects in thirty-two young and thirty-two older adults. Results indicate that self- and close other-referencing similarly enhance general (item) and specific (detail) recognition for both young and older adults relative to the distant other condition. Experiment 2 extended these findings to source memory, with young and older adults encoding verbal information in self-referent, semantic, and structural conditions. Findings suggest that self-referencing provides an age-equivalent boost in general memory and specific memory for specific source details. We conclude that the mnemonic benefits of referencing the self extend to specific memory for visual and verbal information across the lifespan. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Delaying interference enhances memory consolidation in amnesic patients.

Some patients with amnesia are able to retain new information for much longer than expected when the time that follows new learning is devoid of further stimuli. Animal work shows that the absence or delaying of interference improves long-term memory consolidation. Our study suggests that this is also true for at least some patients with amnesia. Retention of new verbal material was significantly higher in a sample of patients with amnesia (N = 12) when interference occurred at the end of a 9-min delay interval than when it occurred in the middle or at the beginning of the interval. Such findings cannot be accounted for by the mere use of explicit short-term memory rehearsal. Any such rehearsal should have been blocked by the interference, irrespective of interference onset, thus leading to poor retention in all three conditions. The current findings suggest that at least some of the severe forgetting observed in amnesia is the product of a disruption of memory consolidation by immediate postlearning interference. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Familiarity enhances visual working memory for faces.

Although it is intuitive that familiarity with complex visual objects should aid their preservation in visual working memory (WM), empirical evidence for this is lacking. This study used a conventional change-detection procedure to assess visual WM for unfamiliar and famous faces in healthy adults. Across experiments, faces were upright or inverted and a low- or high-load concurrent verbal WM task was administered to suppress contribution from verbal WM. Even with a high verbal memory load, visual WM performance was significantly better and capacity estimated as significantly greater for famous versus unfamiliar faces. Face inversion abolished this effect. Thus, neither strategic, explicit support from verbal WM nor low-level feature processing easily accounts for the observed benefit of high familiarity for visual WM. These results demonstrate that storage of items in visual WM can be enhanced if robust visual representations of them already exist in long-term memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Adaptive memory: Survival processing enhances retention.

The authors investigated the idea that memory systems might have evolved to help us remember fitness-relevant information--specifically, information relevant to survival. In 4 incidental learning experiments, people were asked to rate common nouns for their survival relevance (e.g., in securing food, water, or protection from predators); in control conditions, the same words were rated for pleasantness, relevance to moving to a foreign land, or personal relevance. In surprise retention tests, participants consistently showed the best memory when words were rated for survival; the survival advantage held across recall, recognition, and for both within-subject and between-subjects designs. These findings suggest that memory systems are "tuned" to remember information that is processed for fitness, perhaps as a result of survival advantages accrued in the past. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

D-cycloserine enhances memory consolidation in the plus-maze retest paradigm.

Prior undrugged exposure to the elevated plus-maze (EPM) alters future behavioral strategy as well as responsivity to conventional anxiolytic agents. This EPM retest phenomenon appears to be dependent upon learning the spatial configuration of the maze on initial exposure and, in particular, the location of the relatively safe enclosed arms. As posttraining administration of the glycineB receptor partial agonist, D-cycloserine (DCS), has been shown to enhance the consolidation of many forms of memory, we have examined the effects of this compound on the EPM retest effect in male mice. The results of Experiment 1 confirmed that 5 min undrugged exposure to the EPM completed abolishes the anxiolytic efficacy of chlordiazepoxide (CDP; 15 mg/kg) on 24 hr retest. In Experiment 2, posttraining administration of DCS (7.5 and 15 mg/kg), but not CDP (15 mg/kg) or DCS (30 mg/kg), significantly and selectively increased time spent in the enclosed arms (and reciprocally decreased open arm exploration) on 24 hr retest, a finding consistent with an enhancement of consolidation. Experiment 3 used a modified EPM retest protocol to assess the effects of posttraining DCS (15 mg/kg) on behavioral responses to CDP (15 mg/kg) challenge on 24 hr retest. Using a 1-min prior exposure regimen that did not compromise the anxiolytic efficacy of CDP in control mice, the results showed that posttraining administration of DCS abolished the anxiolytic response to CDP challenge. These data strongly suggest that the EPM retest effect involves glycineB/NMDA receptor-dependent neuroplasticity. Further studies will be required to identify the neural circuitry involved. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

First-pass metabolism of ethinyl estradiol in dogs and rats

The contraceptive steroid ethinyl estradiol was extensively metabolized when given orally in solution to dogs. It was thought at first that metabolism occurred exclusively in the liver. However, use of standard equations to predict the oral bioavailability of drugs known to be metabolized by hepatic first pass resulted in significantly higher values than those obtained experimentally. To rationalize the data and to determine whether ethinyl estradiol also is metabolized in the gut wall during absorption, metabolism in rats was studied. The drug was administered in solution intraduodenally, intraportally, and intravenously as a bolus by first-order infusion. The results indicate that, in rats, 40% of the drug is metabolized by the gut wall and 79% of the drug in the portal blood is metabolized by the liver intraduodenal administration.     

Melatonin inhibits naloxone-induced luteinizing hormone release in ovariectomized estrogen-primed rats

The present study aimed to examine the effect of melatonin on naloxone-induced luteinizing hormone (LH) secretion in ovariectomized estrogen-primed rats. A single intracerebroventricular (i.c.v.) injection of naloxone (mu opioid receptor blocker, 15 micrograms) or an intravenous (i.v.) injection of LH-releasing hormone (LHRH, 50 ng/kg) elicited a transient and significant increase in the serum LH concentration within 10 min. While an i.c.v. injection of 100 ng melatonin by itself did not change the basal LH release, it almost completely inhibited the naloxone-induced LH release. Melatonin (10 ng) also significantly reduced the effect of naloxone. However, an i.c.v. injection of 100 ng melatonin did not affect the LHRH-induced LH release. In separate experiments, the effect of melatonin on naloxone-induced pulsatile LH secretion was studied in estrogen-treated rats. A continuous i.v. infusion of naloxone (20 mg/kg/h) induced LH pulses in rats treated i.c.v. with saline. An i.c.v. administration of 100 ng melatonin, which by itself did not affect basal LH secretion, significantly reduced the frequency, but not the amplitude, of LH pulses induced by the naloxone infusion. These results show that melatonin has a suprapituitary site of action to inhibit naloxone-induced LH release, and suggest that melatonin has an effect in inhibiting the activity of the hypothalamic LHRH pulse generator, either directly or indirectly, in female rats.     

Inhibitory effect of progesterone on androgen-induced lordosis in ovariectomized rats

The role of family history as a risk factor of coronary heart disease was explored in the first-degree relatives of 121 female and 586 male survivors of a recent acute myocardial infarction and in those of 130 control women. It was significantly more common for female patients than male patients to have first-degree relatives with coronary artery disease before the age of 65 (76% vs 62%, P = 0.0026). For the sisters of the female patients the cumulative risk of coronary heart disease by the age of 65 years was almost twice that of the sisters of the male patients (25.9% vs 15.8%, P = 0.0123). The risk for the brothers of the females did not significantly differ from that of the brothers of the male patients, but it was 3.5 times that of the brothers of the controls. Thus, while a history of coronary heart disease in first-degree relatives is a risk factor for the disease, the risk is greater in women than in men.