Exposure to estradiol before but not during acquisition of LiCl-induced conditioned taste avoidance accelerates extinction

Estradiol accelerates extinction of LiCl-induced conditioned taste avoidance when it is present continuously before and during acquisition. We have suggested that the effect of estradiol on extinction is due to its illness-associated, rather than learning-associated, properties. If this were the case, then one would expect estradiol to act before but not during acquisition. This expectation is based on previous work showing attenuation of learned taste avoidance when rats are given distal preexposure (greater than 24 h before conditioning) or proximal preexposure (less than 24 h before conditioning) to the illness-inducing agent LiCl before acquisition of a LiCl-induced conditioned taste avoidance. In three separate experiments, estradiol was administered during three different time periods via subcutaneous implantation of a 10-mm estradiol-filled capsule. In each experiment, the extinction of estradiol-treated females was compared to that of females implanted with empty capsules. In the first experiment, female rats were given distal exposure to estradiol before acquisition. Capsules were implanted 11 days before acquisition and were removed 2 days before acquisition. In the second experiment, female rats were given proximal exposure to estradiol before acquisition. Capsules were implanted 2.5 h before LiCl was paired with a sucrose solution and were removed 16.5 h later. In the third experiment, female rats were given exposure to estradiol during acquisition. Capsules were implanted at the same time as LiCl administration and were removed 18 h later. The only estradiol-treated females to show accelerated extinction were those given distal preexposure to estradiol in Experiment 1. These data do not support a learning-associated hypothesis and only partially support an illness-associated hypothesis. The failure to find accelerated extinction following proximal preexposure may reflect an inappropriate choice of the parameters used in the experiment or a difference in the stimulus properties of LiCl and estradiol that allow each to serve as conditioning and preexposure agents in conditioned taste avoidance paradigms [corrected].     

The effects of acute corticosterone on lithium chloride-induced conditioned place aversion and locomotor activity in rats

Acute administration of corticosterone (CORT) facilitates learning in a number of associative paradigms including lithium chloride (LiCl)-induced conditioned taste aversion learning. The present study examined the effects of acute CORT on LiCl-induced conditioned place aversions in male rats. Automated open-fields were partitioned into two chambers distinct in tactile and visual cues. Animals received either LiCl (64 mg/kg, 0.15 M) or saline (NaCl, 0.15 M) followed 10 min later by either CORT (5 mg/kg) or beta-cyclodextrin vehicle (45%) prior to placement in one of the chambers. Control rats received NaCl-Vehicle paired with both chambers. Three experimental groups received either NaCl-CORT, LiCl-Vehicle or LiCl-CORT paired with the preferred chamber and NaCl-Vehicle (control) paired with the non-preferred chamber. During extinction trials, animals were allowed to choose between the two chambers. Locomotor activity and its distribution within the chambers were assessed during both conditioning and extinction trials. CORT administration produced significant increases in a variety of measures of locomotor activity during conditioning trials. During extinction trials both LiCl groups displayed a conditioned place aversion while the NaCl-CORT group did not. In addition, significant increases in vertical activity were recorded in both LiCl groups in the LiCl-paired chamber. Moreover, CORT administration had no effect on LiCl-induced conditioned place aversion as time spent in the LiCl-paired chamber did not significantly differ between LiCl-Vehicle and LiCl-CORT groups. Significant increases in a number of measures of horizontal activity were also observed in both CORT groups. The present study shows that acute CORT administration does not significantly influence LiCl-induced conditioned place aversions and suggests that the facilitatory effects of acute CORT administration on learning are highly context-dependent.     

Experimental dissociation of neural circuits underlying conditioned avoidance and hypophagic responses to lithium chloride

We previously reported that noradrenergic (NA) neurons in the nucleus of the solitary tract (NST) are necessary for exogenous CCK octapeptide to inhibit food intake in rats. To determine whether NST NA neurons also are necessary for lithium chloride (LiCl) to inhibit food intake and/or to support conditioned avoidance behavior, saporin toxin conjugated to an antibody against dopamine beta hydroxylase (DSAP) was microinjected bilaterally into the NST to ablate resident NA neurons. DSAP and sham control rats subsequently were tested for the ability of LiCl (0.15M, 2% body wt) to inhibit food intake and to support conditioned flavor avoidance (CFA). LiCl-induced hypophagia was significantly blunted in DSAP rats, and those with the most extensive loss of NST NA neurons demonstrated the most attenuated LiCl-induced hypophagia. Conversely, LiCl supported a robust CFA that was of similar magnitude in sham control and DSAP rats, including rats with the most extensive NA lesions. A terminal c-Fos study revealed intact LiCl-induced c-Fos expression in the lateral parabrachial nucleus and central amygdala in DSAP rats, despite significant loss of NST NA neurons and attenuated c-Fos activation of corticotropin-releasing hormone-positive neurons in the paraventricular nucleus of the hypothalamus (PVN). Thus, NST NA neurons contribute significantly to LiCl-induced hypophagia and recruitment of stress-responsive PVN neurons but appear to be unnecessary for CFA learning and expression. These findings support the view that distinct central nervous system circuits underlie LiCl-induced inhibition of food intake and conditioned avoidance behavior in rats.     

Amiloride is an ineffective conditioned stimulus in taste aversion learning in C57BL/6J and DBA/2J mice

The epithelial sodium channel (ENaC) blocker amiloride has been shown to increase the behaviorally measured NaCl detection threshold in mice. In this study, a conditioned taste aversion (CTA) paradigm was used to examine whether 100 microM amiloride has a perceptible taste that could contribute to this observed decrease in behavioral responsiveness. Eighty-four C57BL/6J (B6) and 64 DBA/2J (D2) mice were divided into eight groups (n=8-12 per group), in which half received an injection of 0.15 M LiCl (2 mEq/kg) and the other half an equivalent saline injection, in three conditioning trials. The four conditioned stimuli were 100 microM amiloride hydrochloride, water, 0.1 and 0.3 M NaCl. Neither strain demonstrated acquisition of a CTA to amiloride in a brief-access (BA) taste test (5 s trials in the gustometer). Although 0.3 M NaCl is inherently aversive, its pairing with LiCl led to significantly further decreases in licking during the BA test on salt trials in both strains. The D2 strain clearly avoided 0.1 M NaCl, whereas avoidance of this stimulus was more equivocal in B6 mice. The inefficacy of amiloride to serve as a conditioned stimulus in taste aversion learning involving three LiCl pairings suggests that the effects of this ENaC blocker on taste-related behavioral responses to NaCl are likely due to its pharmacological interference with sodium taste transduction.     

The behavioral and somatic effects of ovariectomy and replacement therapy in female collared lemmings (Dicrostonyx groenlandicus)

Reproductive behavior and organ weights in intact estrous and diestrous, and in ovariectomized treated and untreated female collared lemmings (Dicrostonyx groenlandicus) were examined. Sexual behavior of intact diestrous and untreated ovariectomized females was similar, and females in both groups behaved differently from intact estrous females in scores for lordosis and mounting the male. Receptivity was observed in some females within 3 days after the first daily dose of as little as 0.1 μg of estradiol benzoate (EB) and in 83% of all females treated with 0.1 μg or more of EB for 5 days. Vaginal perforation and cornification were related to the dose of EB and length of treatment. The doses of EB used were not related to the lordosis quotient. Ovariectomy and subsequent EB treatment influenced uterine but not preputial gland weight. Adrenal weight was not influenced by ovariectomy or EB treatment, but the increased adrenal weights observed may have been related to the daily pairing of females with males.     

Partner preference of intact and ovariectomized female gray short-tailed opossums (Monodelphis domestica)

Intact, ovariectomized and ovariectomized estradiol (E)-treated female gray short-tailed opossums were placed in a test situation in which they could choose between an intact and a castrated male. Intact females chose to visit intact males first and visited them more frequently and spent more time with intact than with castrated males. Ovariectomized (OVX) females did not show this preference for visiting intact males over castrates. When compared to OVX females with blank implants, OVX females with E implants spent less time with castrated males. Like intact females, OVX and OVX-E-treated females preferred to stay in close proximity to but not actually in the cage of intact rather than castrated males. To our knowledge, this is the first experimental study of partner preference and its relationship to hormonal condition in a female marsupial.     

Progesterone receptor in the forebrain of female gray short-tailed opossums: Effects of exposure to male stimuli

Progesterone receptor immunoreactivity (PRir) in brain areas involved in reproductive behavior in eutherian species was examined for the first time in a female marsupial, the gray short-tailed opossum (Monodelphis domestica, hereinafter, opossum). PRir in nuclei of neurons, measured as area covered by stained nuclei, was seen in the arcuate nucleus (Arc); anteroventral periventricular nucleus (AVPv); bed nucleus of the stria terminalis (BST); medial preoptic area (MPOA), and ventromedial hypothalamus (VMH), but not in control areas adjacent to the hypothalamus or cortex. Female opossums are induced into cytological, urogenital sinus (UGS), estrus by male pheromones and into behavioral estrus, i.e., receptivity, by pairing with a male, and both estradiol (E) and progesterone (P) are involved in induction of receptivity in intact and ovariectomized females. PRir in the AVPv, MPOA, and VMH was very low in females that had never been exposed to males or their scent marks, i.e., naïve anestrous (NVA) females, and either previous or current exposure to males or their scent marks was associated with elevated PRir. PRir was significantly higher in the AVPv and MPOA of anestrous females with previous but no current exposure to males and their scent marks, i.e., experienced anestrous (EXPA) females, than in NVA females, but PRir was significantly lower in the MPOA and VMH of EXPA females than in females that were behaviorally receptive and had recently copulated, i.e., behavioral receptive estrous (BRE) females. PRir was higher in the VMH of both UGS estrous (UGSE) and BRE females compared to that in EXPA animals, but PRir did not differ between UGSE and BRE females in any of the 3 brain areas examined, including the MPOA These results provide evidence that pheromonal induction of estrus and sexual receptivity in opossums is associated with elevation of PRir in the VMH and MPOA and that prior exposure to males or their pheromones, even in the absence of current male stimuli, is associated with persistent elevation of PRir in the AVPv and MPOA.     

General Gregariousness and Specific Social Preferences among Wild Chimpanzees

Wild chimpanzees form temporary parties that vary in size and composition. Previous studies have revealed considerable intraspecific variation in party compositions. We examined patterns of association among age, sex, and reproductive classes of chimpanzees at Ngogo in the Kibale National Park, Uganda. We employed a class-based association index and a randomization procedure to control for confounding factors and to test for differences between classes. Results indicate that males associated with other males significantly more than expected if all classes behaved equivalently, while females generally associated with individuals of the same sex less than expected. To interpret these patterns we used two additional indices that separate associations into two components: general gregariousness and preference for particular classes of associates. Males and estrous females were more gregarious than other classes, while anestrous females were less so. After controlling for general gregariousness, adult males as a class showed no specific preference for associating with each other. Anestrous females preferred each other as party members, and estrous females avoided each other. These results are consistent with previous findings that adult males are more gregarious than females. They diverge from the standard picture of chimpanzee society, however, by suggesting a mutual affinity among anestrous females, but not among adult males as a class.     

Androgen influence on male mouse ultrasounds during courtship

Ultrasonic vocalizations are emitted by adult male mice (Mus musculus) shortly after an adult female or her odor are encountered, possibly as an early part of courtship behavior. Consistent with this hypothesis, it was found that castration of adult male mice increased the latency to first ultrasonic vocalization in response to an adult female. In addition, castrated males, subsequently injected once with 200 μg of testosterone propionate, reduced their latency, whereas oil-injected castrates did not.     

The effect of method of administration on ovarian responses of seasonally anestrous ewes administered gonadotrophin releasing hormone

Mature ewes were treated during the anestrous season with saline (I) or GnRH either intramuscularly in saline (II), subcutaneously in carboxymethylcellulose (CMC) (III) or subcutaneously in gelatin capsules (IV). Fifty μg of GnRH or 1 ml of saline were administered to 22 ewes in experiment 1. In experiments 2 and 3, forty-seven and 10 ewes received 250 μg GnRH or 1 ml of saline. Ewes were bled for progesterone determination prior to treatment and up to 12 or 13 days after treatment. In experiment 3, ovaries were observed via mid-ventral laparotomy 4 days after treatment and ovarian structures recorded. Ewes were classified into one of four progesterone response categories: cyclic, transient, prolonged or no response. The only treatment that changed the progesterone response from the saline-treated controls was GnRH in gelatin capsules. More ewes in this group were classified with a prolonged progesterone response (40%) than in the saline control group (0%). GnRH (in gelatin capsules)-treated ewes in the prolonged progesterone response category had higher concentrations of plasma progesterone than GnRH (in saline or CMC)-treated ewes with a prolonged progesterone response. For the GnRH (in gelatin capsule)-treated ewes, the prolonged progesterone response was similar to progesterone in ewes during the estrous cycle and all ewes in the prolonged progesterone category had corpora lutea (experiment 3). In summary, implanting the GnRH in gelatin capsules subcutaneously in seasonally anestrous ewes increased the ovulation response and enhanced corpus luteum function over ewes administered GnRH in saline intramuscularly.     

Copulatory behavior of adult tamarins (Saguinus fuscicollis) castrated as neonates or juveniles: Effect of testosterone treatment

The sexual interactions of Saguinus fuscicollis males castrated as neonates, at 37 days of age, or prepubertally with adult intact females were studied. Prepubertally castrated males were observed while receiving testosterone, and while being treated with saline. Males castrated neonatally or at 37 days of age were observed while receiving testosterone. Neonatal castrates had previously been studied without hormone treatment and therefore no control condition was included for these animals. Prepubertally castrated males showed Mounts, Mounts with Thrusts, and Sexual Tongue Flicking when treated with saline only. In three of the four males, all measures of sexual behavior increased with testosterone treatment. Neonatally castrated males had failed to display any mounting or thrusting without testosterone treatment during a previous study. During the present study, three of the four males did not respond to testosterone treatment with sexual behavior. The fourth male and one male castrated at 37 days of age displayed some sexual behavior. These results suggest that most neonatally castrated males are not able to respond to testosterone with the activation of copulatory behavior. The findings are consistent with the hypothesis that in callitrichids the sensitive period for behavioral differentiation is shifted into neonatal life. However, some neonatally castrated males show a weak response to testosterone. This may reflect an extended and perhaps partially prenatal period of sensitivity.     

Enhanced consumption of an aversively conditioned taste following the presentation of a “medicine” taste

Rats given presentations of a citric acid solution while recovering from LiCl-induced illness (i.e., a “medicine effect” treatment) subsequently drank more of an aversively conditioned NaCl solution at test, when the NaCl presentation was immediately preceded by citric acid. That is, citric acid passed a summation test of conditioned inhibition. Such an effect was not observed in a group given explicitly unpaired presentations of LiCl and citric acid. It is proposed that enhanced consumption of an aversive taste due to the previous presentation of a “medicine” taste can provide an animal model of human maladaptive behavior in regards to food consumption.     

Sex and estrous cycle differences in the behavioral effects of high-strength static magnetic fields: role of ovarian steroids

Advances in magnetic resonance imaging are driving the development of higher-resolution machines equipped with high-strength static magnetic fields (MFs). The behavioral effects of high-strength MFs are largely uncharacterized, although in male rats, exposure to 7 T or above induces locomotor circling and leads to a conditioned taste avoidance (CTA) if paired with a novel taste. Here, the effects of MFs on male and female rats were compared to determine whether there are sex differences in behavioral responses and whether these can be explained by ovarian steroid status. Rats were given 10-min access to a novel saccharin solution and then restrained within a 14-T magnet for 30 min. Locomotor activity after exposure was scored for circling and rearing. CTA extinction was measured with two-bottle preference tests. In experiment 1, males were compared with females across the estrous cycle after a single MF exposure. Females circled more and acquired a more persistent CTA than males; circling was highest on the day of estrus. In experiment 2, the effects of three MF exposures were compared among intact rats, ovariectomized females, and ovariectomized females with steroid replacement. Compared with intact rats, ovariectomy increased circling; estrogen replacement blocked the increase. Males acquired a stronger initial CTA but extinguished faster than intact or ovariectomized females. Thus the locomotor circling induced by MF exposure was increased in females and modulated by ovarian steroids across the estrous cycle and by hormone replacement. Furthermore, female rats acquired a more persistent CTA than male rats, which was not dependent on estrous phase or endogenous ovarian steroids.     

Potential contribution of prenatal estrogens to the sexual differentiation of mate preferences in mice

The neural mechanisms controlling sexual behavior are sexually differentiated by perinatal actions of gonadal hormones. We recently observed using female mice deficient in alpha-fetoprotein (AFP-KO) and which lack the protective actions of AFP against maternal estrogens, that exposure to prenatal estrogens completely defeminized their potential to show lordosis behavior in adulthood. Therefore, we determined here whether mate preferences were also affected in female AFP-KO mice. We observed a robust preference for an estrous female over an intact male in female AFP-KO mice, which were ovariectomized in adulthood and subsequently treated with estradiol and progesterone, whereas similarly treated WT females preferred the intact male over the estrous female. Gonadally intact WT males preferred the estrous female over the male, but only when visual cues were blocked by placing stimulus animals behind opaque partitions. Furthermore, when given the choice between an intact male and a castrated male, WT females preferred the intact male, whereas AFP-KO females showed no preference. Finally when given the choice between an estrous female and an ovariectomized female, WT males preferred the estrous female whereas AFP-KO females preferred the ovariectomized female or showed no preference depending on whether they could see the stimulus animals or not. Taken together, when AFP-KO females are tested under estrous conditions, they do not show any male-directed preferences, indicating a reduced sexual motivation to seek out the male in these females. However, they do not completely resemble males in their mate preferences suggesting that the male-typical pattern of mate preferences is not solely organized by prenatal estrogens.     

Mating Tactics in Response to Costs Incurred by Mating with Multiple Males in Wild Female Japanese Macaques

We investigated the costs of mating with multiple males in terms of feeding time, traveling distances, sexual proceptivity, and male aggression, for wild female (Macaca fuscata yakui) on Yakushima Island, Japan. We analyzed all-day focal sampling data from 7 females during the mating season (Sept.-Nov. 1996). On days when estrous females copulated with multiple males, they decreased their feeding time to half that of anestrous days, traveled longer distances, showed more proceptive sexual behaviors and received more aggression from subordinate males than on days when they copulated with only the 1st-ranking male. On days when females copulated with only the 1st-ranking male, they showed no difference in feeding time with that of anestrous days, and expended less effort than the above mating pattern because of short traveling distances, diminished sexual proceptivity and a lower frequency of aggression received. The results suggest that the costs of estrous vary according to female sexual proceptivity and the number and social status of mating partners. Female Japanese macaques exhibit a mixed mating strategy over prolonged estrous periods, which may provide females with opportunities to maximize the benefits of copulating with multiple males and to minimize the costs of estrus by mating with only the 1st-ranking male. During an estrous cycle, females may be adjusting efforts for reproduction and survival; i.e., mating vs. feeding.     

An acute social defeat stressor in early puberty increases susceptibility to social defeat in adulthood

Syrian hamsters readily display territorial aggression. If they lose even a single agonistic encounter, however, hamsters show striking reductions in aggressive behavior and increases in submissive behavior, a distinct behavioral change that we have previously termed conditioned defeat. This acute social defeat stressor is primarily psychological and is effective in both males and females. Therefore, we maintain that this procedure presents an ideal model for studying behavioral and physiological responses to social stress. Here, we demonstrate that social avoidance following social defeat is a particularly useful dependent measure because of its sensitivity and stability between sexes and across the estrous cycle. In addition, we demonstrate that peripubertal hamsters exposed to a single, 15 min social defeat exhibit significantly more social avoidance 24 h later when compared with no-defeat controls. Later, defeated and non-defeated hamsters display similar agonistic behavior in adulthood indicating that the peripubertal defeat does not alter adult territorial aggression. After experiencing an additional social defeat in adulthood, however, the hamsters that experienced the pubertal defeat respond to the adult defeat with increased social avoidance when compared with hamsters that were defeated only in adulthood and with no-defeat controls. These data are the first to show that a single social defeat in puberty increases susceptibility to later social defeat in both males and females.     

Can captivity lead to inter-species mating in two Mesocricetus hamster species?

In two closely related species, females generally prefer conspecific males over heterospecific males. We found that estrous (but not diestrous) female Syrian hamsters Mesocricetus auratus prefer the odors of conspecific males to odors of Turkish hamsters Mesocricetus brandti . However, female Syrian hamsters are not aggressive toward male Turkish hamsters and will readily mate with them. We hypothesize that many generations in captivity led to a reduction in females' ability to avoid inter-species mating, possibly related to the heightened sexual receptivity observed in Mesocricetus hamsters in captivity. To test this hypothesis, we replicated a study carried out with female Turkish hamsters soon after the current laboratory stock of this species was established. In that study, female Turkish hamsters showed lordosis toward male Syrian hamsters in only 20% of interactions and attacked heterospecific males in 80% of the pairings. Using animals descended from that original colony (after many generations in captivity and certain episodes of inbreeding), 100% of female Turkish hamsters mated with heterospecific males and none showed aggression toward heterospecific males. Thus female avoidance of inter-specific mating may be affected by captive rearing conditions.     

Taste aversions in the ontogeny of the rat

The characteristics of acquisition and extinction of conditioned taste aversion (CTA) were studied in rats of both sexes and various ages by pairing of saccharin solution consumption with discomfort (LiCl intoxication, rotation). Pairing of saccharin consumption with LiCl in adult rats led to acquisition of CTA, more profound in male rats than in female ones. In rats of both sexes 30 days old, a profound CTA, comparable in intensity with CTA of adult male rats was acquired. In 2 months after acquisition of CTA in adult rats its magnitude did not change, while in rats of the junior group which by that time had reached puberty, CTA was reduced in females and did not change in males. Pairing of saccharin intake and rotation led to acquisition of CTA only in rats 30 days old. The role of external factors in duration of retention of CTA acquired by pairing of saccharin solution consumption with LiCl injection was studied in male and female rats 1 and 3.5 months old. In all cases CTA was extinguished much sooner in home cages than in experimental chambers, and in the elder group sex dimorphism was found: in both situations CTA disappeared sooner in female rats. The obtained data allow to suggest modulating influences of hormonal background and of contextual stimuli on CTA acquisition and retention.     

Duration of androgen treatment modifies behavioral response to arginine vasotocin in Taricha granulosa

Five and eighteen days after surgery, injection of arginine 8-vasotocin (AVT) stimulated clasping behavior in castrated controls (unimplanted or cholesterol-implanted) but not in androgen-implanted, castrated newts (Taricha granulosa). Conversely, AVT injected 33 days after castration increased the incidence of courtship behavior of androgen-implanted males, but not of unimplanted castrates. Plasma androgen concentration of androgen-implanted castrates (as determined by radioimmunoassay) was maintained at a level typical of intact males at the peak of the breeding season. Because the AVT-androgen interaction could occur at the level of the pituitary gland, castrated, androgen-implanted newts were hypophysectomized and injected with AVT. Hypophysectomy did not abolish the behavioral response to AVT.     

Estrous female goats use testosterone-dependent cues to assess mates

In a promiscuous species like the domestic goat (Capra hircus), in which maternal investment is greater than paternal investment, a female may mate selectively with a more-fit male to improve her reproductive fitness. Testosterone (T) controls a large suite of male-typical behaviors and morphological characteristics. High T concentrations may be energetically costly or even detrimental to survival; thus, preventing lower quality males from falsely advertising their fitness. Three preference studies were conducted to examine if females use T-dependent cues to assess potential mates. For Experiment 1, females were given a choice between a pair of morphologically similar males, bucks (intact males) and stags (post-pubertally castrated males), during the breeding and non-breeding seasons. In both seasons, females preferred the bucks compared to stags. In Experiment 2, females were given a choice between bucks, stags and wethers (pre-pubertally castrated males) during the non-breeding season. For some comparisons, castrated males received 25 mg testosterone propionate (TP) or were untreated. Females preferred TP-treated males compared to untreated males and showed no preference when given a choice between either two TP-treated or two untreated males. In Experiment 3, females were given a choice between a pair of bucks and a pair of stags treated with 25 mg TP during monthly tests in the breeding season. At each monthly test, females preferred the males with higher T concentrations near the time of the behavior test. These studies suggest that females use T-dependent cues to assess potential mates, and T concentrations may indicate a male's overall fitness.