Dietary Soy Supplements Produce Opposite Effects on Anxiety in Intact Male and Female Rats in the Elevated Plus-Maze.

The effects of 2 popular, commercially available soy phytoestrogen supplements on anxiety in male, diestrus female, and proestrus female rats were examined with an elevated plus-maze. Both of the soy supplements were anxiolytic in proestrus females but anxiogenic in males as determined by time spent in the open arms. No effect of diet was seen in the diestrus females. The observed changes in anxiety were not because of altered levels of gonadal hormones, as serum estrogen and progesterone levels were unaffected by diet in the females. The results suggest that the soy supplements have sex- and cycle-specific effects on anxiety. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Aggressive behaviors in adult SF-1 knockout mice that are not exposed to gonadal steroids during development.

Sex hormones are a major factor responsible for the development of sex differences. Steroidogenic factor 1 (SF-1) is a key regulator of gonadal and adrenal development, and SF-1 knockout mice (SF-1 KO) are born without gonads and adrenal glands. Consequently, these mice are not exposed to gonadal sex steroids. SF-1 KO pups die shortly after birth due to adrenal deficiency. In the present study, SF-1 KO mice were rescued by neonatal corticosteroid injections followed by adrenal transplantations on day 7-8 postnatally. Control mice received corticosteroid injections and were gonadectomized prior to puberty. Mice were observed interacting with ovariectomized hormone primed females and gonad-intact males. In the absence of sex steroid replacement, adult SF-1 KO mice were significantly more aggressive than control mice in tests with stimulus females. After testosterone treatment, control males displayed significantly more aggression towards male intruders than control female mice, or male and female SF-1 KO mice, suggesting a developmental role of gonadal hormones in the expression of aggressive behavior and affirming SF-1 KO mice as a behavioral model to investigate affects of fetal gonad deficiency. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of neonatal RU486 on adult sexual, parental, and fearful behaviors in rats.

Exposure to gonadal hormones during perinatal life influences later behavior. The finding that sex differences exist in progestin receptor expression in the perinatal rat brain suggests differential sensitivity of male and female brains to progesterone (C. K. Wagner, A. N. Nakayama, & G. J. De Vries, 1998). Because these sex differences are in neural sites that influence sexually differentiated sexual, parental, and fearful behaviors in adults, this study examined the effects of administering the progestin receptor antagonist RU486 for the first 10 days after birth on these behaviors in adulthood. Neonatal RU486 significantly reduced sexual behavior in males but did not impair reproduction in females. Neonatal RU486 did not affect parental responses of virgin rats exposed to pups (sensitization) but reduced fear in the elevated plus-maze in both sexes. Treatment of pups with RU486 affected neither mother–litter interactions nor plasma testosterone levels in males during or after treatment. These results suggest that neonatal exposure to progesterone, in addition to androgens and estrogens, influences behavioral development in rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Chronic neonatal nicotine increases anxiety but does not impair cognition in adult rats.

Developmental nicotine exposure has been implicated in the association between maternal smoking and adverse outcomes in offspring. The 3rd trimester of human pregnancy is equivalent to the 1st postnatal week in rodents; both are periods of active brain growth during which nicotinic acetylcholine receptors are transiently upregulated. Chronic neonatal nicotine (CNN; 6 mg/kg/day) from postnatal Days 1 to 7 was given orally to rat pups to evaluate long-term behavioral effects. Males and females were tested as adolescents or as young adults. CNN significantly decreased center time, ambulatory behavior, and rearing in the open-field test and decreased the number of entrances and time spent in the open arm of the elevated plus-maze in both sexes and ages. CNN did not change performance in the T maze or in the water maze in adult males or females. Motor coordination was not altered. In summary, CNN had long-term effects on anxiety-like behavior but did not affect spatial learning and memory functions. This finding is particularly important when evaluating the benefits of nicotine-replacement therapies during human pregnancies, which may improve smoking cessation rates but could result in long-term behavioral consequences. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Open-field and avoidance behavior after neostriatal lesions in male and female rats.

The behavioral effects of lesions of the anterodorsal or posteroventral parts of the caudate-putamen were studied in 2 experiments with a total of 115 male and 101 female adult albino Holtzman rats that were gonadectomized or left untreated prior to brain surgery. Anterodorsal (ADC) lesions consistently impaired acquisition of 1-way avoidance behavior and tended to interfere with the development of a 2-way avoidance response; comparable effects were observed in gonadectomized and intact Ss of both sexes. By contrast, ADC lesions increased activity in the open field only in intact females and increased rearing only in ovariectomized females. Posteroventral caudate (PVC) lesions caused transient aphagia and adipsia in both sexes but did not consistently affect open-field activity or the acquisition of 1-way avoidance responses by either sex. These lesions profoundly impaired acquisition of shuttle box avoidance responses by intact males. By contrast, castrated males and intact and ovariectomized females with PVC lesions avoided normally in the shuttle box. Results suggest that localization of behavioral functions within the striatum differs with the sex of the S, in part because of activational effects of gonadal hormones. (37 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sex hormones differentially regulate isoforms of UDP-glucuronosyltransferase

PURPOSE: To investigate the role of sex hormones in the regulation of UDP-glucuronosyltransferase (UGT). METHODS: We examined liver from adult, prepubertal, gonadectomised and gonadectomised plus hormone replaced rats of both sexes. Immunohistochemistry and immunoblots were performed using a polyclonal UGT antibody to a number of family 1 and family 2 UGT isoforms. Northern blot analysis was performed utilising cDNA probes to family 1 and family 2 isoforms. RESULTS: Immunohistochemistry demonstrated variations in intensity and distribution of staining in the hormonally manipulated rats. Immunoblots showed variations in individual band intensity between rat groups. Immunoblots using a more specific antibody (anti-17 beta-hydroxysteroid UGT, which recognises UGT2B3 and UGT2B2) demonstrated marked differences between male and female rats and significant alterations after gonadectomy and testosterone replacement in the male rats. In northern analysis, UGT2B3 and 2B1 mRNA were significantly higher in adult males than females, and in prepubertal males compared to prepubertal females. In male rats, gonadectomy resulted in a 45-53% reduction in UGT2B3 and 2B1 levels respectively, which increased significantly with testosterone treatment to greater than normal adult levels. No change in UGT2B3 or 2B1 occurred after gonadectomy in females. In contrast, UGT1*1 mRNA tended to be higher in adult female and prepubertal female rats than in their male counterparts. In females, gonadectomy resulted in significant up-regulation of UGT1*1, while gonadectomy plus oestradiol treatment resulted in markedly reduced levels. UGT1*1 mRNA was not significantly altered by gonadectomy in males. CONCLUSIONS: This study demonstrates the differential effects of sex hormones on the expression of isoforms from the two phylogenetically distinct UGT families.     

N-methyl-D-aspartate-stimulated increases in intracellular calcium exhibit brain regional differences in sensitivity to inhibition by ethanol

To determine what effect ovariectomy and the accompanying sudden loss of circulating gonadal hormones has on spatial learning performance in the adult rat, two groups of rats were tested on the Lashley III simple alley maze following surgery. Ovariectomized animals were compared with a control group of animals that underwent laparotomy at the same time. The ovariectomized group evidenced superior performance on the maze task, as measured by latency to reach goal (running times) and error scores. It is suggested that this finding provides further evidence for the role of gonadal steroid hormones in the manipulation of functions related to learning and memory, especially in the hippocampus.     

Prenatal ethanol exposure differentially alters behavior in males and females on the elevated plus maze

Rodents prenatally exposed to ethanol demonstrate hypothalamic-pituitary-adrenal and behavioral hyperactivity to a variety of stressful situations. The present study examined both behavioral and corticosterone (CORT) responses to the elevated plus maze (+-maze), an anxiety- or fear-provoking task. Sprague-Dawley male and female offspring from fetal ethanol-exposed (E), pair-fed (PF), and ad libitum-fed control (C) groups were tested at 60 to 90 days of age. In experiment 1, behavior was measured in animals exposed to the +-maze for 5 min on two consecutive days; 2 weeks later, both behavioral and CORT responses were measured in animals confined to the open and closed arms of the maze for 20 min. In experiment 2, animals were placed in an open field (OF) for 5 min before a single 5-min exposure to the +-maze. Factor analysis of the scored behaviors from the two experiments indicated two main factors, designated "exploration" and "fear." E males and females both exhibited higher levels of exploratory behaviors when placed directly on the +-maze from their homecages without prior exposure to the OF, compared with C males and females. In addition, when confined to the closed arms of the +-maze, E males and females demonstrated higher levels of activity, compared with C males and females. After OF exposure, however, both E males and females demonstrated lower levels of exploratory behaviors than C males and females, and E females also had increased CORT levels, compared with PF and C females. Interestingly, E females, but not E males, showed an increase in fear-related behaviors on the +-maze, compared with controls, regardless of prior OF exposure. These data demonstrate that prenatal ethanol exposure may differentially affect both behavioral and hormonal responses of males and females in an aversive behavioral task and suggest that there may be a sex difference in the sensitivity of the mechanism(s) underlying these responses.     

Clinical and radiological assessment of proximally coated stems in growth in total hip replacement]

Although cocaine is a powerful reinforcer, it has been reported to produce anxiety in humans and anxiogenic-like behavior in animals. The goal of this study was three-fold: (1) to determine the doses of cocaine that induce anxiogenic-like behavior in the elevated plus-maze in rats, (2) to determine if cocaine-associated contextual cues are capable of eliciting anxiogenic-like behavior in the absence of the drug, and (3) to identify possible mechanisms through which cocaine-associated cues affect behavior in the elevated plus-maze. Measurement of the amount of time that the animals spend exploring the open arms of the maze provides a sensitive index of anxiogenic-like behavior in rats. In experiment 1, rats were injected with 10 mg/kg, 20 mg/kg, or 30 mg/kg cocaine HCl or saline for 6 days. On day 6, the rats were tested in the elevated plus-maze 25 min after injection with cocaine or saline. The animals chronically treated with the three doses of cocaine exhibited a dose-dependent increase in anxiogenic-like behavior in the elevated plus-maze, compared to the saline-treated group. In experiment 2, cocaine-induced (30 mg/kg) conditioning was achieved using a simple contextual design. On the final day of the experiment (day 6), after 5 days of conditioning, the rats were exposed for 25 min to the cocaine-associated contextual cues, then placed in the elevated plus-maze. Animals that had been exposed to cocaine-associated contextual cues prior to being placed in the elevated plus-maze exhibited a significant increase in anxiogenic-like behavior compared to the control groups. However, pretreatment of the rats with the CRF antagonist, alpha-helical CRF9-41 (1 microg, i.c.v.), on the test day, prior to exposure to cocaine-associated contextual cues, attenuated the subsequent anxiogenic-like behavioral response in the elevated plus-maze (experiment 3). The results suggest that contextual cues associated with repeated treatment with 30 mg/kg cocaine are capable of eliciting anxiogenic-like behavior in the absence of the drug and that CRF mediates the expression of anxiogenic-like behaviors in the elevated plus-maze following exposure to cocaine-associated cues. The conditioned anxiogenic action elicited by cocaine-associated cues may have relevance for understanding the complex addictive nature of this drug and some of the clinical phenomena related to its use.     

Sex differences in investigatory and grooming behaviors of laboratory rats (Rattus norvegicus) following exposure to novelty.

Prior research suggested that during exposure to novel stimuli, rodent investigation and self-grooming behaviors may be sexually dimorphic and interact with ambient illumination. To test this notion we compared the behavior of adult male and female groups of Long-Evans hooded rats in normal room lighting (860 lx) and in very dim, red light (0.2 lx) following exposure to a novel juvenile conspecific. Illuminance level had little or no effect, but investigatory and subsequent self-grooming behaviors of males were substantially greater than those of females, and females engaged in greater ambulatory activity than did males. In a second experiment adult males and females were exposed to a novel inanimate object. No reliable sex differences were observed. We conclude that social novelty, as provided by exposure to a juvenile conspecific, stimulates greater investigation and postinvestigatory self-grooming than exposure to a novel inanimate object and that exposure to novel conspecifics presents a useful method for the investigation of sex differences, gonadal hormone effects, and interactions of hormones with neurotransmitter systems governing motor control systems. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Manipulation of gonadal hormones in neonatal rats alters the morphological response of cortical neurons to brain injury in adulthood.

The authors examined the effects of sex and neonatal hormones on the response of pyramidal cells (Layer III, parietal cortex) to injury of the medial frontal cortex in the adult rat. At birth, males were gonadectomized (GDX) or sham-operated. Females were given testosterone (T) or oil injections. In adulthood, rats that had been left intact at birth were GDX, and they then received bilateral medial frontal cortex lesions or sham surgery. Rats not exposed to T at birth exhibited losses of dendritic arbor (males GDX at birth) or dendritic spine density (oil-treated females). Compensation after cortical injury is dependent on the rat's sex and history of exposure to gonadal steroids. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Development of sociosexual approach behavior in male laboratory rats.

Studied approach behavior toward male and female incentives in male Sprague-Dawley rats during development from prepuberty to adulthood. Both incentives were approached, but the magnitude of the response changed with age. At 70 days of age, the typical adult approach response was evident: the female was contacted for the better part of a session and the male incentive was contacted very little. The time for the appearance of this contact response was not obviously influenced by prepubertal experience in intact males or by the presence of gonadal hormones in neonatally castrated males. However, the magnitude of the preference for the female appeared to be affected by such treatment. (8 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neonatal androgenic stimulation and adult sexual behavior in male and female golden hamsters.

In an experiment with 48 male and 48 female golden hamsters, neonatally and adult castrated males as well as neonatally androgenized and nonandrogenized females were tested for both mounting and lordosis behaviors during treatment with either testosterone or ovarian hormones. Neonatal androgenization facilitated mounting behavior in adult Ss administered either testosterone or ovarian hormones and suppressed lordosis behavior in adult ovarian-hormone-treated Ss. Early androgen effects on the display of lordosis behavior during adult testosterone treatment were complex and varied with the exact timing of perinatal endogenous or exogenous androgenization. Species differences in hormone-behavior relationships and the possible role of perinatal androgenization in the development of rodents' ability to aromatize androgens are discussed. (29 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Estrogen-progesterone regulation of nest-building and incubation behavior in ovariectomized ring doves (Streptopelia risoria).

Determined the role of ovarian hormones in the induction of nest-building (tucking) and incubation behavior in female doves by systemic injections of estrogen, or progesterone, or estrogen combined with progesterone, or oil in 40 reproductively experienced, ovariectomized Ss. Combined estrogen and progesterone treatment was the most effective hormone regimen for eliciting both behavior patterns in females and also facilitated these behaviors in their 40 untreated mates. Differences in role of the gonadal progesterone in male and female doves are discussed. (23 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Repeated exposure to stress across the childhood-adolescent period alters rats' anxiety- and depression-like behaviors in adulthood: The importance of stressor type and gender.

This research tests the hypothesis that specific forms of adversity in early life map onto behavioral signs analogous to depression versus anxiety in later life. Male and female rats were exposed to either severe sporadic stress or chronic mild stress during the childhood-adolescent period, and their behavior was tested in adulthood. Males in the severe sporadic stress group showed exaggerated anxiety-related behaviors, as indicated by increases in shock-probe burying and escape-like responses (jumps) from the open arms of the elevated plus-maze. Females exposed to severe sporadic stress displayed no change in burying behavior but did display increases in escape behavior. These same females also exhibited behaviors analogous to depression that manifested as decreased sucrose consumption. The chronic mild stress regime produced effects only in females, including reduced burying, decreased sucrose consumption, and an exaggerated corticosterone response to cold-water immersion stress. Findings reiterate the importance of early life experience to the development of adult psychopathologies and emphasize the need to consider both the type of early experience and gender differences in these analyses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Illumination has no effect on rats' behavior in the elevated plus-maze

Male Wistar rats Shoe:Wist(Shoe) were tested in the elevated plus-maze under three different illumination levels (30, 300, and 900 lx). It was found that illumination did not change percentage of time spent in closed arms, number of closed arm entries, or time spent on open arms, or total arm entry. This confirms earlier findings that rat's behavior in the elevated plus-maze is independent of light levels.     

Sex difference in the control of scent-marking behavior in the Mongolian gerbil (Meriones unguiculatus).

Investigated the importance of the gonadal hormones in the control of the scent-marking behavior of 51 adult female Mongolian gerbils. Gonadectomy did not lead to the decrease in marking which had been expected from previous studies with males. The 2nd experiment was a longitudinal study of the development of scent marking in 36 female Ss. Ss were ovariectomized or given sham operations at 22 days of age. Gonadal hormones were not required for the development of marking. In both experiments morphological measures of the ventral sebaceous scent gland and the presence of the vaginal orifice were affected by gonadectomy. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neonatal sex hormones have 'organizational' effects on the hypothalamic-pituitary-adrenal axis of male rats

Sex hormones have activational effects on the hypothalamic-pituitary-adrenal (HPA) axis in adulthood: For example, corticosterone release is influenced by gonadal status. These experiments investigated whether sex hormones have organizational effects on the HPA axis of male rats: Do sex hormones have relatively permanent effects on its development? In adults, both neonatal (neoGDX) and adult gonadectomy (adult GDX) resulted in elevated corticosterone (CORT) levels in response to stress compared to intact rats. Five days of testosterone propionate (TP) replacement was not as effective at attenuating CORT levels in neoGDX rats as in adult GDX rats. Neonatal GDX elevated corticosterone binding globulin (CBG) levels, whereas adult GDX was without effect. In Experiment 2 the effects of neonatal gonadectomy and neonatal treatment with either TP, estradiol benzoate (EB), or oil vehicle was examined. Despite 14 days of hormone replacement, neoGDX showed elevated CORT levels in response to stress compared to all other groups. A single neonatal dose of TP or EB in neoGDX rats eliminated the increased responsiveness. Neonatal TP and EB were without effect in sham-operated rats. Plasma CBG levels were elevated in neoGDX groups regardless of neonatal hormone treatment. Corticosteroid receptor binding levels were examined in various brain areas and the pituitary in two groups most different in their androgen experience: NeoGDX and shams that did not receive treatments as adults. NeoGDX had lower levels of glucocorticoid receptor, and higher levels of mineralocorticoid receptor binding in the pituitary. No other receptor differences were found. These experiments suggest that neonatal sex hormones influence the sensitivity of the HPA axis to sex hormones in adulthood and, thus, that they have organizational effects in addition to activational effects on HPA function.     

Behavioural pharmacological characteristics of honokiol, an anxiolytic agent present in extracts of Magnolia bark, evaluated by an elevated plus-maze test in mice

Honokiol, a neolignane derivative of Magnolia bark, has central depressant action and, at much lower doses, anxiolytic activity. We have investigated the characteristics of the behavioural effects of honokiol by means of an elevated plus-maze test. In the plus-maze test a single oral dose of 20 mg kg(-1) honokiol significantly prolonged the time spent in the open arms of the maze, suggesting anxiolytic effect. Moreover, when honokiol was administered daily for seven days and the plus-maze test was conducted 3 or 24 h after the last administration, significant prolongation of the time in the open arms was manifested even for doses of 0.2 mg kg(-1). The maximum effect was observed for doses of 0.5 mg kg(-1). Honokiol at any dose in both single and repeated administration schedules caused neither change in motor activity nor disruption of traction performance. Orally administered diazepam, 0.5-2 mg kg(-1), caused dose-dependent prolongation of the time spent in the open arms of the maze with a significant increase in motor activity at 1 mg kg(-1), and dose-dependent disruption of traction performance. The changes in the plus-maze performance after treatment for seven days with 0.2 mg kg(-1) honokiol and after a single treatment with 1 mg kg(-1) diazepam were almost equivalent. The effect of honokiol (0.2 mg kg(-1), treatment for seven days) was inhibited by subcutaneous flumazenil (0.3 mg kg(-1)) and (+)-bicuculline (0.1 mg kg(-1)) and by intraperitoneal CCK-4 (50 microg kg(-1)) and caffeine (30 mg kg(-1)). The anxiolytic effect of diazepam (1 mg kg(-1)) was also inhibited by flumazenil and bicuculline. However, the combined administration of diazepam with caffeine enhanced the effect, and diazepam completely reversed the effect of CCK-4. These results suggest that, in contrast with diazepam, honokiol selectively induces an anxiolytic effect with less liability of eliciting motor dysfunction and sedation or disinhibition. The combined effects of the drug also revealed that the mechanism of anxiolytic effect of honokiol is partially different from that of diazepam.     

Long-lasting effects of neonatal stimulation on the behavior of rats.

The present study aimed to analyze the effects of neonatal stimulation on species-specific behaviors (defensive reactions to a predator and social interactions) in adult male and female rats. Handling and an unpredictable sequence of aversive stimuli were applied to male and female pups from the 1st to the 10th day after delivery; behavioral inhibition, aggression, and sexual behavior were evaluated in adulthood. Results showed that either neonatal handling or aversive stimulation decreased behavioral inhibition in a novel and potentially harmful situation (open field with a predator) in both male and female rats and increased maternal aggressive behavior. Sexual behavior in both males and females decreased, which could affect reproductive capability. The results could cast doubts on the generalization of beneficial effects of neonatal stimulation on the behavior of adult rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)