Renewal of conditioned fear in male and female rats.

Pavlovian extinction reduces the performance of conditioned responses and occurs when the conditioned stimulus (CS) is repeatedly presented in the absence of the unconditioned stimulus (US). However, when the CS is experienced in a context that is different from the extinction context, there is a recovery of the conditioned response, a phenomenon known as renewal. There is some evidence that the renewal of appetitive conditioning is influenced by sex, with females failing to exhibit renewed responding. Further, there is recent evidence that renewal of fear might also not occur in female rats. In both appetitive and fear preparations, the lack of renewal in females has been postulated to be related to cycling ovarian hormones. Therefore, in Experiments 1 and 2, we directly compared fear renewal in males and females (Experiment 1) as well as ovariectomized (OVX) females (Experiment 2) when conditioning occurred in Context A, extinction in B, and testing in A (ABA renewal). Experiments 3 and 4 examined renewal when conditioning and extinction occurred in A and testing occurred in B (AAB renewal). In all experiments, renewal was not significantly different between male and female rats. Further, in Experiments 2 and 4, renewal did not differ between males, intact females, and OVX females. Additionally, in each experiment, there was no evidence that context excitation and/or inhibition contributed to renewal; instead suggesting that renewal was controlled by an occasion-setting mechanism. Overall, these results suggest little evidence for the role of sex in renewal of conditioned freezing and also indicate that cycling ovarian hormones have little role in the strength of renewal in female rats. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Acute stress facilitates habitual behavior in female rats.

Instrumental behavior can reflect the influence of goal-directed and habitual systems. Contemporary research suggests that stress may facilitate control by the habitual system under conditions where the behavior would otherwise reflect control by the goal-directed system. However, it is unclear how stress modulates the influence of these systems on instrumental responding to achieve this effect, particularly in females. Here, we examine whether a mild psychogenic stressor experienced before acquisition training (Experiment 1), or prior to the test of expression (Experiment 2) would influence goal-directed and habitual control of instrumental responding in female rats. In both experiments, rats acquired an instrumental nose-poke response for a sucrose reward. This was followed by a reinforcer devaluation phase in which half the rats in Stressed and Non-Stressed conditions received pairings of the sucrose pellet with illness induced by lithium chloride until they rejected the pellet when offered. The remaining rats received a control treatment consisting of pellets and illness on separate days (Unpaired). Control by goal-directed and habitual systems was evaluated in a subsequent nonreinforced test of nose poking. The results of Experiment 1 indicated that the Non-Stressed Paired group reduced nose-poking compared to the Unpaired controls, identifying the response as goal directed, whereas the Stressed Paired and Unpaired groups made a similar number of nose pokes identifying the response as habitual despite a similar amount of training. Results from Experiment 2 indicated habitual control of nose-poke responding was present when stress was experienced just prior to the test. Collectively, these data suggest that stress may facilitate habitual control by altering the relative influence of goal-directed and habitual processes underpinning instrumental behavior. These results may be clinically relevant for understanding the contributions of stress to dysregulated instrumental behavior in compulsive pathologies.

Levonorgestrel maintains goal-directed behavior in habit-trained intact female rats.

Hormonal contraceptives are utilized by millions of women worldwide. However, it remains unclear if these powerful endocrine modulators may alter cognitive function. Habit formation involves the progression of instrumental learning as it goes from being a conscious goal-directed process to a cue-driven automatic habitual motor response. Dysregulated goal and/or habit is implicated in numerous psychopathologies, underscoring the relevance of examining the effect of hormonal contraceptives on goal-directed and habitual behavior. This study examined the effect of levonorgestrel (LNG), a widely used progestin-type contraceptive, on the development of habit in intact female rats. Rats were implanted with subcutaneous capsules that slowly released LNG over the course of the experiment or cholesterol-filled capsules. All female rats underwent operant training followed by reward devaluation to test for habit. One group of females was trained at a level that is sub-threshold to habit, while another group of females was trained to a level well over the habit threshold observed in intact females. The results reveal that all sub-threshold trained rats remained goal-directed irrespective of LGN treatment, suggesting LNG is not advancing habit formation in female rats at this level of reinforcement. However, in rats that were overtrained well above the threshold, cholesterol females showed habitual behavior, thus replicating a portion of our original studies. In contrast, LNG-treated habit-trained rats remained goal-directed, indicating that LNG impedes the development and/or expression of habit following this level of supra-threshold to habit training. Thus, LNG may offset habit formation by sustaining attentional or motivational processes during learning in intact female rats. These results may be clinically relevant to women using this type of hormonal contraceptive as well as in other progestin-based hormone therapies.

Effects of sex and retention interval on the retrieval and extinction of auditory fear conditioning.

Fear memory retrieval is relevant to psychiatric disorders such as post-traumatic stress disorder (PTSD). One of the hallmark symptoms of PTSD is the repeated retrieval and re-experiencing of the initial fear memory even long after the traumatic event has occurred. Women are nearly twice as likely to develop PTSD following a trauma than men, thus sex differences in the retrieval of fear memories is highly relevant for understanding the development and maintenance of PTSD. In the current study, we aimed to examine sex differences in the retrieval and extinction of either recent or remote fear memories. To do so, we conditioned male and female rats either 1 day (recent) or 28 days (remote) prior to testing retrieval and extinction. While there was no effect of sex or retention interval on initial retrieval, we found that remotely conditioned females exhibited higher rates of freezing than remotely conditioned males in later retrieval/extinction sessions, suggesting a sex difference in the retrieval and/or extinction of remote, but not recent, fear memories. Overall, these results are the first to demonstrate a sex difference in the extinction of remote fear memory, and this may contribute to the differential expression of fear-related disorders like PTSD in men and women.

Cyclic estrogen and progesterone during instrumental acquisition contributes to habit formation in female rats.

Habit formation is thought to involve two parallel processes that are mediated by distinct neural substates: one that suppresses goal-directed behavior, and one that facilitates stimulus-response (S-R) learning, which underscores habitual behavior. In previous studies we showed that habitual responding emerges early during instrumental training in gonadally-intact female, compared to male, rats. The present study aimed to determine the role of ovarian hormones during instrumental acquisition in the transition from goal-directed to habitual behavior in female rats. Ovariectomized (OVX) female rats were given subcutaneous silastic capsules that released low levels of 17-ß estradiol (E2) to maintain estrogen receptor availability. Rats were assigned to one of three hormone treatment conditions: no additional hormone replacement (Control group), replacement with high E2 (High E2 group), or replacement with high E2 followed by progesterone (High E2 + P4 group). Hormone replacement occurred twice during acquisition to mimic natural hormone fluctuations. At test, the Control and High E2 groups demonstrated responding that was sensitive to devaluation by lithium chloride-induced illness, indicating goal-directed behavior. In contrast, the High E2 + P4 group exhibited a pattern of devaluation-insensitive, habitual responding, that suggested the suppression of goal-directed processes. In a follow-up experiment, similar procedures were conducted, however during acquisition, OVX rats were given cyclic high E2 plus medroxy-progesterone (MPA), a form of progesterone that does not metabolize to neuroactive metabolites. In this group, goal-directed behavior was observed. These data indicate that habit formation is not facilitated in low estrogen states, nor in the presence of cyclic high E2. However, cyclic high E2, together with progesterone during acquisition, appears to facilitate the early emergence of habitual responding. Furthermore, these data suggest that a neuroactive progesterone metabolite, like allopregnanolone, in combination with high cyclic E2, supports this phenomenon.

Dopamine sensitization by methamphetamine treatment prior to instrumental training delays the transition into habit in female rats.

Early in instrumental learning, behavior is goal-directed and sensitive to changes in the value of the instrumental outcome. With sufficient repetition, responding becomes insensitive to changes in outcome value, or habitual. We have previously found that females transition into habit over a distinct range of training from 120 to 160 reinforced responses. This low level of instrumental training is markedly less than what has been shown to support habitual responding in male rats. To begin to investigate the early development of habit in females, we conducted a series of experiments in which we pretreated female rats with methamphetamine (METH) with the aim of sensitizing central dopamine, a major modulator of striatal function, prior to instrumental nose-poke training at the beginning and at the endpoint of the transition range in females. Following training, we tested for sensitivity to reinforcer devaluation (RD), which was conducted by repeatedly pairing reinforcers previously earned during training with lithium chloride (LiCl)-induced illness. As a counterpoint, a series of similar experiments was conducted separately in male rats. Additionally, in order to ascertain the validity of using nose-poke as an instrumental response, we compared sensitivity to devaluation between the Pavlovian approach towards the food magazine and the nose-poke response. In females, Vehicle groups responded in a habitual manner at both training levels (120 and 160 reinforced responses), whereas METH groups remained sensitive to devaluation. This suggests that increasing central dopamine delays habit formation in female rats. In male rats, Vehicle groups demonstrated goal-directed responding following training with 120 and 320 reinforced responses, and marginally goal-directed responding,with 160. METH-pretreated males were sensitive to devaluation at the 120 and 160 training levels, however, following more extended training to 320 reinforced responses, METH-pretreated males responded in a habitual manner, indicating that increasing central dopamine can advance habit formation in male rats. Overall, these results suggest that METH pretreatment maintains goal-directed responding in female rats when they are typically transitioning to habitual control of instrumental behavior and can advance habit formation in male rats given sufficient instrumental training. In addition, we found differential RD sensitivity of the nose-poke response used during instrumental training compared to Pavlovian approach towards the food magazine, confirming that there is a distinction between these two behaviors and that nose-poking is a valid instrumental response.

Social subordination alters estradiol-induced changes in cortico-limbic brain volumes in adult female rhesus monkeys.

Women have a higher risk of developing stress-related disorders compared to men and the experience of a stressful life event is a potent risk-factor. The rodent literature suggests that chronic exposure to stressors as well as 17ß-estradiol (E2) can result in alterations in neuronal structure in corticolimbic brain regions, however the translation of these data to humans is limited by the nature of the stressor experienced and issues of brain homology. To address these limitations, we used a well-validated rhesus monkey model of social subordination to examine effects of E2 treatment on subordinate (high stress) and dominant (low stress) female brain structure, including regional gray matter and white matter volumes using structural magnetic resonance imaging. Our results show that one month of E2 treatment in ovariectomized females, compared to control (no) treatment, decreased frontal cortex gray matter volume regardless of social status. In contrast, in the cingulate cortex, an area associated with stress-induced emotional processing, E2 decreased grey matter volume in subordinates but increased it in dominant females. Together these data suggest that physiologically relevant levels of E2 alter cortical gray matter volumes in females after only one month of treatment and interact with chronic social stress to modulate these effects on brain structure.

Effects of social subordination and oestradiol on resting-state amygdala functional connectivity in adult female rhesus monkeys.

Preclinical studies demonstrate that chronic stress modulates the effects of oestradiol (E2) on behaviour through the modification of the amygdala and the medial prefrontal cortex (mPFC) neuronal structure. Clinical studies suggest that alterations in amygdala functional connectivity (FC) with the mPFC may be associated with stress-related phenotypes, including mood and anxiety disorders. Thus, identifying the effects of stress and E2 on amygdala-mPFC circuits is critical for understanding the neurobiology underpinning the vulnerability to stress-related disorders in women. In the present study, we used a well-validated rhesus monkey model of chronic psychosocial stress (subordinate social rank) to examine effects of E2 on subordinate (SUB) (i.e. high stress) and dominant (DOM) (i.e. low stress) female resting-state amygdala FC with the mPFC and with the whole-brain. In the non-E2 treatment control condition, SUB was associated with stronger left amygdala FC to subgenual cingulate (Brodmann area [BA] 25: BA25), a region implicated in several psychopathologies in people. In SUB females, E2 treatment strengthened right amygdala-BA25 FC, induced a net positive amygdala-visual cortex FC that was positively associated with frequency of submissive behaviours, and weakened positive amygdala-para/hippocampus FC. Our findings show that subordinate social rank alters amygdala FC and the impact of E2 on amygdala FC with BA25 and with regions involved in visual processing and memory encoding.

Female rats express habitual behavior earlier in operant training than males.

Habitual behavior can be advantageous by increasing the availability of cognitive resources for use in other tasks. However, habitual behaviors are problematic when they are coopted to prolong the maladaptive responding present in several psychopathologies such as substance abuse, dysregulated fear responding in posttraumatic stress disorder, and obsessive-compulsive disorder. Although sex differences exist in the occurrence or progression of these psychopathologies, there are no studies that compare the development of habitual behavior systematically in male and female animals. In the present study, male and female rats were identically trained on a variable interval 30-s (VI 30-s) schedule of reinforcement to nose-poke for sucrose pellet reinforcers. Subsequently, the sucrose was devalued in one half of the animals by pairing its presentation with injections of lithium chloride (LiCl) to induce nausea, thus conditioning a taste aversion. Habitual behavior was operationalized as continued operant responding in an extinction test following devaluation of the sucrose reinforcer. Successful devaluation was confirmed with both a consumption and reacquisition test. Given identical training to 240 sucrose pellets, female rats demonstrate habitual behavior whereas male rats remain goal-directed. Additionally, females are habitual after 200 or 160 reinforcers earned on a VI 30-s schedule, but remain goal-directed at 120 and 80 reinforcers on this schedule. These data suggest that behavioral flexibility may be compromised in female rats compared to males due to accelerated habit formation in females. These results are important because sex differences are present in several psychopathologies, which may be related to differences in the development of habitual behavior. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Socially Housed Female Macaques: a Translational Model for the Interaction of Chronic Stress and Estrogen in Aging.

PURPOSE OF REVIEW: Estrogen's role in cognitive aging remains unclear. Despite evidence implicating stress in pathological aging, the interaction of stress with estrogen on cognition in older women has received little attention, and few animal models exist with which to examine this interaction. RECENT FINDINGS: We present evidence that aging socially subordinate female macaques that experience chronic psychosocial stress constitute a suitable model to investigate this. First, we review studies showing that estrogen modulates cognition in animal models, as well as studies demonstrating that estrogen's action on certain types of cognition is impaired by stress. Next, we discuss data showing that middle-aged socially subordinate female macaques exhibit distinct stress-induced phenotypes, and review our investigations indicating that estrogen modulates behavior and physiology differently in subordinate female monkeys. We conclude that socially housed female macaques represent a translational animal model for investigating the interplay of chronic stress and estrogen on cognitive aging in women.

Pituitary adenylate cyclase activating polypeptide (PACAP), stress, and sex hormones.

Stressor exposure is associated with the onset and severity of many psychopathologies that are more common in women than men. Moreover, the maladaptive expression and function of stress-related hormones have been implicated in these disorders. Evidence suggests that PACAP has a critical role in the stress circuits mediating stress-responding, and PACAP may interact with sex hormones to contribute to sex differences in stress-related disease. In this review, we describe the role of the PACAP/PAC1 system in stress biology, focusing on the role of stress-induced alterations in PACAP expression and signaling in the development of stress-induced behavioral change. Additionally, we present more recent data suggesting potential interactions between stress, PACAP, and circulating estradiol in pathological states, including PTSD. These studies suggest that the level of stress and circulating gonadal hormones may differentially regulate the PACAPergic system in males and females to influence anxiety-like behavior and may be one mechanism underlying the discrepancies in human psychiatric disorders.

The Effects of Prior Stress on Anxiety-Like Responding to Intra-BNST Pituitary Adenylate Cyclase Activating Polypeptide in Male and Female Rats.

Chronic or repeated exposure to stressful stimuli can result in several maladaptive consequences, including increased anxiety-like behaviors and altered peptide expression in anxiety-related brain structures. Among these structures, the bed nucleus of the stria terminalis (BNST) has been implicated in emotional behaviors as well as regulation of hypothalamic-pituitary-adrenal (HPA) axis activity. In male rodents, chronic variate stress (CVS) has been shown to increase BNST pituitary adenylate cyclase activating polypeptide (PACAP) and its cognate PAC1 receptor transcript, and BNST PACAP signaling may mediate the maladaptive changes associated with chronic stress. Here, we examined whether CVS would sensitize the behavioral and/or endocrine response to a subthreshold BNST PACAP infusion. Male and cycling female rats were exposed to a 7 day CVS paradigm previously shown to upregulate BNST PAC1 receptor transcripts; control rats were not stressed. Twenty-four hours following the last stressor, rats were bilaterally infused into the BNST with a normally subthreshold dose of PACAP. We found an increase in startle amplitude and plasma corticosterone levels 30 min following intra-BNST PACAP infusion in male rats that had been previously exposed to CVS. CVS did not enhance the startle response in cycling females. Equimolar infusion of the VPAC1/2 receptor ligand vasoactive intestinal polypeptide (VIP) had no effect on plasma corticosterone levels even in previously stressed male rats. These results suggest that repeated exposure to stressors may differentially alter the neural circuits underlying the responses to intra-BNST PACAP, and may result in different anxiety-like responses in males and females.

17ß-estradiol replacement in ovariectomized female rats slows set 1 dorsolateral striatial-dependent learning and enhances learning of set 2 in an extradimensional set-shifting paradigm.

The role of estrogen in extradimensional set-shifting was evaluated with replacement of 17ß-estradiol (E2) in ovariectomized (OVX) female rats. Rats were reinforced with food when they entered an arm of a plus-maze that was distinguished by visual and/or tactile cues (Set 1). In Set 2, reinforcement was shifted to construct a new association between food and visual/tactile cues that were different from Set 1. The purpose of using this extradimensional set-shifting task was to differentiate the effect of acute or continuous E2 on the dorsolateral (DLS) versus dorsomedial (DMS) striatum and medial prefrontal cortex (mPFC), because Set 1 and 2 learning, respectively, are associated with these particular brain regions. Results showed that compared to controls, acute E2-replaced female rats required more training trials to reach criterion in Set 1. Moreover, E2-replaced females showed a significant delay in the rate of acquisition of Set 1 learning compared to controls. In Set 2 there were no group differences in perseverative errors, which are reduced by mPFC activation, or when learning took place in a previously reinforced arm, a DMS-mediated effect. Despite this, control females required more training trials to learn Set 2 compared to Set 1, suggesting that prior learning in Set 1 interfered with Set 2 performance in non-E-replaced rats. In contrast, E2 groups learned Set 2 in fewer training trials than Set 1. These data suggest that E2 facilitates set shifting, apart from any apparent enhancement of DMS or mPFC function, perhaps by interfering with DLS-mediated Set 1 learning.

Place and Response Learning in the Open-field Tower Maze.

This protocol describes how the Open-field Tower Maze (OFTM) paradigm is used to study spatial learning in rodents. This maze is especially useful for examining how rats learn to use a place- or response-learning to successfully navigate in an open-field arena. Additionally, this protocol describes how the OFTM differs from other behavioral maze paradigms that are commonly used to study spatial learning in rodents. The OFTM described in this article was adapted from the one previously described by Cole, Clipperton, and Walt (2007). Specifically, the OFTM was created to test spatial learning in rodents without the experimenter having to consider how "stress" might play a role as a confounding variable. Experiments have shown that stress-alone can significantly affect cognitive function(1). The representative results section contains data from an experiment that used the OFTM to examine the effects of estradiol treatment on place- and response-learning in adult female Sprague Dawley rats(2). Future studies will be designed to examine the role of the hippocampus and striatum in place- and response-learning in the OFTM.

Effects of continuous vs. cycling estrogen replacement on the acquisition, retention and expression of place- and response-learning in the open-field tower maze.

Estrogen has been shown to either enhance or impair learning and memory in female rats. The use of different experimental paradigms or estrogen treatment regimens may contribute to these disparate findings. In order to assess the effect of different estradiol (E2) treatments on several aspects of cognition, we trained ovariectomized female rats with either continuous, cycling, or vehicle E2 replacement, in an open-field tower maze task (OFTM) designed to test reference memory in a low-stress environment. In addition, in order to compare two distinct learning and memory systems, rats were trained to use either a dorsolateral striatum-based response type learning or a hippocampal-based place type learning to solve the maze. Results showed that cyclic, but not continuous, E2 replacement facilitated the acquisition of spatial memory in place-learners. Neither E2 regimen affected acquisition in response-learners. Additionally, when all experimental groups were performing at asymptote, rats were evaluated for performance stability by changing the location of their start position in the OFTM. Both regimens of E2 disrupted the expression of spatial memory in place-learners following the novel start position. However, E2 replacement protected ovariectomized female rats from the disruption of memory expression following a start position change in response-learners. Additionally all experimental groups performed equally well when tested following a 21-day period during which rats were absent from the maze. These results suggest that E2 fluctuation is particularly important in the acquisition of hippocampal-mediated spatial learning, and that hippocampal-based memory may be subject to disruption following environmental change, while striatum-based memory is subject to protection.

PACAP in the BNST produces anorexia and weight loss in male and female rats.

Recent gene association studies have implicated pituitary adenylate cyclase-activating peptide (PACAP) systems in several psychiatric disorders associated with stressor exposure, and we have argued that many of the behavioral consequences of repeated stressor exposure may depend on the expression of PACAP in the bed nucleus of the stria terminalis (BNST). One behavioral consequence of the activation of stress systems can be anorexia and subsequent weight loss, and both the activation of central PACAP systems as well as neuronal activity in the BNST have also been associated with anorexic states in rodents. Hence, we investigated the regulation of food and water intake and weight loss following BNST PACAP infusion. BNST PACAP38 dose-dependently decreased body weight, as well as food and water intake in the first 24 h following infusion. Because different BNST subregions differentially regulate stress responding, we further examined the effects of PACAP38 in either the anterior or posterior BNST. Anterior BNST PACAP38 infusion did not alter weight gain, whereas posterior PACAP38 infusion resulted in weight loss. PACAP38 infused into the lateral ventricles did not alter weight, suggesting that the effects of BNST-infused PACAP were not mediated by leakage into the ventricular system. These data suggest that PACAP receptor activation in posterior BNST subregions can produce anorexia and weight loss, and corroborate growing data implicating central PACAP activation in mediating the consequences of stressor exposure.

Exercise-associated changes in the corticosterone response to acute restraint stress: evidence for increased adrenal sensitivity and reduced corticosterone response duration.

Exercise promotes stress resistance and is associated with reduced anxiety and reduced depression in both humans and in animal models. Despite the fact that dysfunction within the hypothalamic pituitary adrenal (HPA) axis is strongly linked to both anxiety and depressive disorders, the evidence is mixed as to how exercise alters the function of the HPA axis. Here we demonstrate that 4 weeks of voluntary wheel running was anxiolytic in C57BL/6J mice and resulted in a shorter time to peak corticosterone (CORT) and a more rapid decay of CORT following restraint stress. Wheel running was also associated with increased adrenal size and elevated CORT following systemic administration of adrenocorticotropic hormone. Finally, the HPA-axis response to peripheral or intracerebroventricular administration of dexamethasone did not suggest that wheel running increases HPA-axis negative feedback through GR-mediated mechanisms. Together these findings suggest that exercise may promote stress resilience in part by insuring a more rapid and shortened HPA response to a stressor thus affecting overall exposure to the potentially negative effects of more sustained HPA-axis activation.

Gonadal hormones and voluntary exercise interact to improve discrimination ability in a set-shift task.

Exercise has been demonstrated to improve multiple facets of health, including cognitive function. Rodent studies have suggested that exercise has robust effects on the hippocampus and on tasks that require the hippocampus. However, studies of the effects of exercise in humans often focus on the benefits to cognitive processes that engage areas outside of the hippocampus, such as executive function. Additionally, when exercise's cognitive benefits are examined, consideration of both males and females, and gonadal hormones, is rarely made. Here we looked at the interaction of gonadal hormones and exercise in terms of the ability of male and female rats to learn to discriminate rewarded from unrewarded arms in a T maze based on either brightness (white vs. black) or texture (rough vs. smooth) and then to set-shift (a measure of executive function), where this required discrimination is based on the opposite dimension. Gonadectomized or intact males and females had access to running wheels for 2 weeks before being tested. Intact males and females given access to unlocked running wheels performed better at the initial discrimination (Set 1) compared with intact males and females with locked running wheels but not at the set shift (Set 2). No advantage of exercise was observed in gonadectomized rats.

Dietary variety is associated with larger meals in female rhesus monkeys.

The complex, interacting influences on eating behavior and energy expenditure prevent elucidation of the causal role of any single factor in the current obesity epidemic. However, greater variety in the food supply, particularly in the form of highly palatable, energy-dense foods, has likely made a contribution. This study was undertaken to test the hypothesis that greater dietary variety is associated with greater caloric intake within individual meals consumed by free-feeding, socially-housed female rhesus monkeys. Meal patterns were assessed during two, two-week dietary phases. One phase consisted of a choice between a standard chow diet and a highly palatable diet (HPD). The other phase consisted of access to the chow only. Food intake for each subject was recorded continuously using previously validated, automated feeders, and a meal was defined based on a minimum kilocalorie requirement and a minimum inter-meal interval. During the choice condition, animals electively consumed mixed meals that incorporated both diets as well as other meals that consisted exclusively of a single diet - chow-only or HPD-only. Animals consumed the most calories per meal when the meal was comprised of both the chow and HPD, which differed in caloric density, flavor, and texture. Interestingly, however, there was no significant difference in the amount of calories consumed as HPD-only meals in the choice condition compared to meals in the chow-only, no choice condition, suggesting consumption of a single food during a meal, regardless of palatability, provides a constant sensory experience that may lead to more rapid habituation and subsequent meal cessation. Additionally, during the dietary choice condition, animals consumed fewer calories in the form of chow-only meals. Thus, the present results suggest that limiting dietary variety, regardless of palatability, may be a useful strategy for weight loss in overweight and obese individuals by reducing caloric intake within individual meals.

Estrogen enhances the retention of spatial reference memory in the open field tower task, but disrupts the expression of spatial memory following a novel start position.

Estrogen's (E) involvement in cognition has been difficult to characterize; numerous studies show that E can both enhance and impair learning and memory. One difficulty may be that experimental paradigms often examine only a single aspect of E's involvement in cognition, for example, the role E plays in the expression of memory after learning has taken place. In addition, the effect of aversive and/or stressful features inherent to many cognitive tests may contribute to the contradictory findings. The present experiment aims to examine the effect of estradiol (E2) on several elements of cognition in a specific experimental setting. We investigated the within-subject effects of long-term E2 replacement in ovariectomized (OVX) female rats on the acquisition and retention of a hippocampal-mediated spatial reference memory task in a familiar non-threatening environment. Results show that E2-replaced rats and OVX sham-replaced rats acquired the ability to navigate an open-field tower maze in order to obtain a food reward at the same rate. Subsequent to acquisition, both E2-replaced and OVX rats performed the task at comparable levels. However, following a 21-day retention interval, non-replaced rats exhibited a significant impairment in spatial memory when returned to the maze environment, while E2-replaced rats exhibited no change in maze performance. When the OVX group was performing once again at asymptote, test trials were administered during which the rats were placed in a non-experienced start location within the maze. This novel condition significantly reduced correct responses in E2-replaced females whereas OVX controls remained unaffected. These results suggest that while the presence of E2 is not important for acquisition of spatial memory in a safe familiar environment, it improves retention of spatial memory. Data further suggests that E2 disrupts the expression of spatial reference memory following an alteration of the test conditions sustaining a habitual response, possibly by the induced emotionally-arousing state of stress.