Latent inhibition is affected by phase of estrous cycle in female rats

Estrogen has been shown to have a strong modulatory influence on several types of cognition in both women and female rodents. Latent inhibition is a task in which pre-exposure to a neutral stimulus, such as a tone, later impedes the association of that stimulus with a particular consequence, such as a shock. Previous work from our lab demonstrates that high levels of estradiol (E2) administered to ovariectomized (OVX) female rats abolishes latent inhibition when compared to female rats with low levels of E2 or male rats. To determine if this E2-induced impairment also occurs with the natural variations of ovarian hormones during the estrous cycle, this behavior was investigated in cycling female rats. In addition, pre-pubertal male and female rats were also tested in this paradigm to determine if the previously described sex differences are activational or organizational in nature. In a latent inhibition paradigm using a tone and a shock, adult rats were conditioned during different points of the estrous cycle. Rats conditioned during proestrus, a period of high E2 levels, exhibited attenuated latent inhibition when compared to rats conditioned during estrus or metestrus, periods associated with low levels of E2. Moreover, this effect is not seen until puberty indicating it is dependent on the surge of hormones at puberty. This study confirms recent findings that high E2 interferes with latent inhibition and is the first to show this is based in the activational actions of hormones.     

Social isolation inhibits male-like sexual behavior in female hamsters

In the female golden hamster, Mesocricetus auratus, group housing permits the expression of male-like behavioral patterns including mounting and pelvic thrusting toward an estrous stimulus female. Sixty percent of females housed in groups of five showed these behaviors, while singly housed females were rarely observed to show mounting or thrusting. Females weaned at 19 or 35 days of age did not differ in their tendencies to show male-like behavioral patterns. Virtually all observations of mounting and pelvic thrusting behaviors were made on days when the females being tested were in behavioral estrus. These findings differ from previous studies which have reported that masculine behavioral patterns are rare in normal female hamsters. In previous studies females that were evaluated were typically not in behavioral estrus and were not housed for long periods of time with other intact females. Social factors interact with hormonal state to contribute to the expression of male-like behaviors in female hamsters.     

Ovarian steroids enhance object recognition in naturally cycling and ovariectomized, hormone-primed rats

Learning and memory processes may be influenced by fluctuations in steroid hormones, such as estrogens and progestins. In this study, we have used an animal model to investigate the effects of endogenous fluctuations in ovarian steroids in intact female rats and effects of administration of ovarian steroids to ovariectomized rats for non-spatial, working memory using the object recognition task. Performance in this task relies on cortical and hippocampal function. As such, serum, cortical, and hippocampal concentrations of estradiol (E2), progesterone (P4), and P4's metabolite, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP), were measured by radioimmunoassay. Experiment 1: Rats in behavioral estrus, compared to those in diestrus or estrus, spent a greater percentage of time exploring a novel object concomitant with increases in serum E2, P4, and 3alpha,5alpha-THP levels. Regression analyses revealed that there was a significant positive relationship between E2 levels in the hippocampus and 3alpha,5alpha-THP levels in the hippocampus and cortex and performance in this task. Experiment 2: Administration of E2 and/or P4 immediately post-training increased the percentage of time spent exploring the novel object and produced levels of E2, P4, and 3alpha,5alpha-THP akin to that of rats in behavioral estrus. Experiment 3: Post-training administration of selective estrogen receptor modulators, including 17beta-E2, propyl pyrazole triol, and diarylpropionitrile increased the percentage of time spent exploring the novel object compared to vehicle-administration. Experiment 4: Post-training P4 or 3alpha,5alpha-THP administration, compared to vehicle, increased the percentage of time spent exploring the novel object and produced P4 and/or 3alpha,5alpha-THP levels within the physiological range typically observed for rats in behavioral estrus. Experiment 5: If post-training administration of E2 and/or P4 was delayed one hour, no enhancement in object recognition was observed. Together, these results suggest that E2 and progestins can have mnemonic effects through actions in the cortex and/or hippocampus.     

Responsiveness to estrous chemostimuli in male rats (Rattus norvegicus) of different ages

Previous findings indicate that Norway rats (Rattus norvegicus) respond differentially to estrous chemostimuli in early infancy and that adult male sexual responsiveness to such chemostimuli depends on infantile experience with suckling odors (Fillion & Blass, in press). The development of behavioral responsiveness to estrous chemostimuli in male rats from late infancy to adulthood was examined in this study. Preweanling, adolescent, and adult males were observed for 20 min in the presence of an anesthetized estrous or an anesthetized diestrous female. This was, for adolescent and adult subjects, the first heterosexual encounter since weaning. Rats in each age-group responded differentially according to female state, but in distinct, age-related ways. Preweanling spent more time investigating the female's body if she was estrous. Adults expressed the same affinity but by more focused investigation directed perivaginally. Adolescents showed no female-directed bias but groomed themselves more if the female was estrous. These data identify developmental continuities and discontinuities in male rat behavior toward sexually receptive females.     

Rule abstraction, item memory, and chunking in rat serial-pattern tracking

Two studies used a stimulus tracking paradigm to test whether rats are sensitive to the rule-based formal properties of structured serial patterns. Hooded rats tracked 16-element patterns of flashing lights by pressing levers under an array of 6 indicator lights. In Experiment 1, rats tracked a pattern similar to one previously used with human subjects and yielded remarkably similar results. More errors and response omissions occurred at boundaries of structural "chunks" than within chunks, and errors often reflected anticipation of the next chunk or extrapolation of the preceding chunk. In Experiment 2, temporal "phrasing" cues encouraged different groups to encode a pattern as a series of either "runs" or "trills." Differential placement of pauses induced rats to encode different rule-based representations of the pattern. Results indicate that under appropriate conditions rats may encode a representation of formal structure when they learn organized response patterns.     

Social dominance, reproduction, and release of the maturation-delaying chemosignal in the urine of female house mice (Mus musculus)

Five experiments were performed to investigate the effects of social status in groups of female mice on reproduction and on the release or urinary chemosignals that accelerate or delay the onset of sexual maturation in young females. Treatment of young female mice with urine from bottom-ranking mice in groups of 5 adult females resulted in delays in puberty comparable to those produced by treatment with urine pooled from females housed at moderate to high densities. Treatment of young females with urine from top-ranking females from the same groups resulted in ages for puberty not different from those of control females treated with water. There was an interaction between the social rank of a female and the stages of the estrous cycle with respect to the presence in the urine of chemosignals from grouping that delay puberty and estrus that accelerate puberty. Within groups of 5 adult mice, top-ranking females were in estrus more frequently than bottom-ranking females. Individually caged adult females treated with urine from top-ranking females were in estrus more frequently than females treated with urine from bottom-ranking females. When grouped females were separated into individual cages and mated, there was differential reproductive success: More top-ranking females conceived and bore litters than bottom-ranking females. Bottom-ranking females produced more female pups, relative to top- and middle-ranking females.     

Influence of personality,age, sex,and estrous state on chimpanzee problem-solving success

Despite the importance of individual problem solvers for group- and individual-level fitness, the correlates of individual problem-solving success are still an open topic of investigation. In addition to demographic factors, such as age or sex, certain personality dimensions have also been revealed as reliable correlates of problem-solving by animals. Such correlates, however, have been little-studied in chimpanzees. To empirically test the influence of age, sex, estrous state, and different personality factors on chimpanzee problem-solving, we individually tested 36 captive chimpanzees with two novel foraging puzzles. We included both female (N = 24) and male (N = 12) adult chimpanzees (aged 14–47 years) in our sample. We also controlled for the females’ estrous state—a potential influence on cognitive reasoning—by testing cycling females both when their sexual swelling was maximally tumescent (associated with the luteinizing hormone surge of a female’s estrous cycle) and again when it was detumescent. Although we found no correlation between the chimpanzees’ success with either puzzle and their age or sex, the chimpanzees’ personality ratings did correlate with responses to the novel foraging puzzles. Specifically, male chimpanzees that were rated highly on the factors Methodical, Openness (to experience), and Dominance spent longer interacting with the puzzles. There was also a positive relationship between the latency of females to begin interacting with the two tasks and their rating on the factor Reactivity/Undependability. No other significant correlations were found, but we report tentative evidence for increased problem-solving success by the females when they had detumescent estrous swellings.     

Acceleration and delay of sexual maturation in female house mice (Mus domesticus) by urinary chemosignals: mixing urine sources in unequal proportions

Urine from male mice, from estrous female mice, and from pregnant or lactating female mice accelerate first vaginal estrus in females, whereas urine from grouped female mice delays first estrus. Nine experiments were used to test the effects of treatment of young female mice with urinary chemosignals that influence the onset of first estrus using unequal proportions of urine from the different sources. At ratios of 10-20 parts acceleratory chemosignal to 1 part delay chemosignal the acceleratory effect overrides the delay chemosignal, and the mice attain first estrus at earlier ages than controls. Ratios of about 4 to 1 up to 7 to 1 result in mean ages for puberty that are not accelerated or delayed relative to controls. Over a modest range of actual dose amounts of urine, the ratio effects are the same regardless of the actual quantities of urine employed in treating test females.     

Influence of housing on the consequences of chronic mild stress in female rats

The chronic mild stress (CMS) paradigm was developed to model anhedonia in animals. The repeated administration of a series of unpredictable, mild stressors attempts to mimic the daily stress associated with the onset of clinical depression in humans. Male animals are predominantly used in these investigations despite significant, well-documented sex differences in human depression. In this study, the CMS procedure was modified to be more ecologically relevant to female animals. The effects of stress on sucrose preference, social interaction, rate of weight gain, and regularity of the estrous cycle in female Sprague-Dawley (SD) rats were evaluated in both single- and paired-housed rats, during 3 weeks each of baseline, CMS, and post-CMS phases. The results indicate that only single-housed rats exposed to stressors have a reduced rate of weight gain, significantly attenuated sucrose preference levels, and increased social interaction scores during the CMS phase of the study. Housing condition more than exposure to stress appeared to contribute to the disruption of estrous cycling in some animals. These data suggest that housing affords some protection from the negative consequences of CMS, at least in female rats, and that lack of social interaction in the single-housing condition may render females more vulnerable to stress-related illnesses. The development of paradigms that model human depression should emphasize sex-specific differences.     

The effects of early handling on the partial reinforcement extinction effect and the partial punishment effect in male and female rats

Handled (Day 1-22) and non-handled infantile Wistar rats were tested in maturity for the partial reinforcement extinction effect (PREE) and the partial punishment effect (PPE). In Experiments 1 and 2, mature male and female rats were trained to run in an alley for food reward on a 1-trial/day schedule. In the PREE paradigm (Experiment 1), the partially reinforced group (PRF) received reinforcement on a quasi-random 50% schedule, while the continuously reinforced group (CRF) received reinforcement on every trial. In the test stage, both groups were given extinction training. In the PPE paradigm (Experiment 2), the partially punished (PP) group received, together with continuous reinforcement, shocks on a quasirandom 50% schedule, while the continuously reinforced group was reinforced on every trial. In test, all animals were given both reinforcement and shock on every trial. In Experiment 1, PREE—i.e. increased resistance to extinction in the PRF as compared to the CRF group—was more pronounced in the handled animals. More specifically, no PREE was obtained in the non-handled males, and in the non-handled females the PREE was reduced compared to the handled females. The results of Experiment 2 revealed no effect of handling or sex on PPE, that is, increased resistance to punishment in the PP group as compared to the CRF group was evident in all four conditions. In Experiment 3, handled and non-handled male rats were tested for the PREE using a multi-trial procedure in an operant chamber. PREE was obtained in the handled but not in the non-handled animals. The implications of these results for the differential effects of handling on male and female rats and the distinction between the PREE and PPE paradigms are discussed.     

Sexual free behavior in male rats (Rattus norvegicus).

Male rats (Rattus norvegicus) were given continuous access to estrous female rats for 24 hr each day for 10 days. During the first 12 hr, the rats achieved an average of 10 ejaculations, followed by a 1- to 2-day recovery period with little sexual activity. During the last 7 days, the rats maintained a reasonably stable equilibrium level of 3 ejaculations per day. These occurred predominantly during the dark phase of the diurnal cycle, they frequently occurred in a cluster, and they usually occurred shortly after the introduction of a novel estrous female. Except for quantitative differences, these results are generally consistent with conventional research but systematically extend the generality of the results to the context of the free behavior situation. The availability of sexual activity had no appreciable effect on food and water intake, but it did decrease the amount of running activity.     

The effects of a flavour - toxicosis pairing upon long-delay, flavour aversion learning

Mackintosh (1973) has suggested that rats readily associate flavours with illnesses in cue-to-consequence studies because they have already learned that changes in internal states are unrelated to changes in external stimuli. An implication of this suggestion is that learned predispositions may also subserve the ability of rats to form long-delay, flavour-illness associations. Six experiments tested this idea by examining the strengths of aversions in a delayed flavour-toxicosis paradigm after exposure to a paired or unpaired relation between another flavour and toxicosis. Exposure to a paired relation enhanced the strengths of subsequently established flavour aversions (Experiment I). The enhanced aversions were associative in origin (Experiment II), observed with delays of 3 h and 1·5 h in, respectively, a forward (Experiment III) and backward (Experiment IV) delayed conditioning paradigm and with a 10-day interval between the flavour-toxin pairing and the delayed paradigm (Experiment V). The enhanced aversions, however, were removed by the extinction of the original flavour aversion prior to the delayed flavour-toxin pairing (Experiment VI). The results supported the idea that the ability of the rat to form long-delay, flavour-illness associations reflects an associative history involving flavours and internal changes and were discussed in terms of Mackintosh's (1975) theory of the mechanism underlying stimulus selection. The effects of a flavour-toxicosis pairing upon long-delay, flavour aversion learning.     

Incentive shift in the rat following training to resist punishment

An incentive shift paradigm was used to test for the similarity of fear and frustration. In Experiment 1, rats trained to resist electric shock punishment showed neither a negative contrast effect nor any performance decrement when reward was shifted from 10 to one pellet. Experiment 2 replicated the basic findings of Experiment 1, but also showed that punishment training did not influence the magnitude of performance shift for animals receiving increases in reward magnitude. Finally, Experiment 3 additionally found that rats sensitized to punishment showed an increase in negative contrast effect. These results support the hypothesized functional similarity between conditioned fear and conditioned frustration with learned persistence or sensitivity to one generalizing to the other as suggested by Amsel's (1972) theory of persistence.     

Modulation of male mouse sniff, attack, and mount behaviors by estrous cycle-dependent urinary cues

Modulation of male urogenital sniff, attack, and mount behaviors by urinary cues from female mice (SJL/J) was assessed in two experiments. Experiment 1 examined the efficacy of urine from ovariectomized and intact females in modulating the behavior of sexually experienced and inexperienced males vis-à-vis the control substance, water. It was found that urine from ovariectomized females showed no behavior-modulating properties, whereas urine from intact females decreased attack but increased sniff and mount behaviors in male mice. These findings are indicative of ovarian-dependent chemosignals contained in the urine of only intact females. Prior sexual experience had no effect on behavior of males when exposed to urine from ovariectomized females. Sniff and mount behaviors were, however, increased when sexually experienced males were exposed to urine from intact females. Using sexually inexperienced males, Experiment 2 assessed the chemosignal activity of urine from females in each of four estrous phases. It was determined that urine from proestrous and estrous females increased sniff and mount behaviors and decreased attack behavior. Urine from metaestrous females was shown to possess only sniff-inducing and mount-reducing chemosignal properties. Urine from females in diestrous lacked attack- and mount-modulating chemocues but may possess a sniff-inducing chemosignal.     

Attenuation of latent inhibition after compound pre-exposure: Associative and perceptual explanations

Three experiments used rats as subjects and the conditioned emotional response (CER) paradigm to examine the effect of pre-exposure to a compound stimulus on the extent of latent inhibition to an element of that compound. In Experiment 1a a group of rats exposed to a compound that comprised a tone and a click exhibited less latent inhibition to the tone than did a group that had received pre-exposure to the tone in isolation. Experiment 1b showed that pre-exposure to the tone/click compound also resulted in an attenuation of latent inhibition to the click relative to a group that was pre-exposed to the click in isolation. Experiment 2 demonstrated that latent inhibition to the tone was left intact following pre-exposure to the tone in compound with a light. This pattern of results seems to be most plausibly explained in terms of the presence and absence of generalization decrement following compound pre-exposure.     

Inhibiting progesterone metabolism in the hippocampus of rats in behavioral estrus decreases anxiolytic behaviors and enhances exploratory and antinociceptive behaviors

Blocking progesterone’s metabolism to 5α -pregnan-3α -ol-20-one (3α ,5α -THP) with finasteride, a 5α -reductase inhibitor, and effects on anxiolytic, exploratory, and antinociceptive behaviors of rats in behavioral estrus were examined. Rats in behavioral estrus received finasteride systemically (SC), to the hippocampus, or to control implant sites, the nucleus accumbens (NA) or ventral tegmental area (VTA), and were tested in horizontal crossing, open-field, elevated plus-maze, emergence, holeboard, social interaction, tailflick, pawlick, and defensive freezing tasks. Finasteride, SC or intrahippocampally, reduced 3α ,5α -THP in the hippocampus relative to vehicle implants or finasteride to the NA or VTA. Systemic or intrahippocampal finasteride decreased central entries in the open field and open-arm time on the elevated plus-maze and increased freezing in response to shock relative to vehicle. Finasteride to the hippocampus decreased emergence latencies and increased social interaction, pawlick, and tailflick latencies relative to all other groups. Finasteride to the hippocampus of rats in behavioral estrous decreased anxiolysis and enhanced exploration and analgesia. In summary, these data demonstrate that decreases in anxiolytic behavior of behavioral estrous rats can be produced by reductions in 3α ,5α -THP in the hippocampus, which suggest that elevations in 3α ,5α -THP in the hippocampus may give rise to anxiolysis seen during behavioral estrus.     

Sexual experience and preference for males or females in the female rat

The influence of sexual experience on preference behavior was investigated in adult female rats. In the first experiment, preference behavior for sexually active males versus estrous females was investigated in female rats who were experienced with mounting behavior. Preference of these mount experienced females was compared to preference of females who were naive in this respect. Mount experience with estrous females induced a female-directed preference in ovariectomized female rats, irrespective of whether the females were treated with OIL or with testosterone-propionate (500 micrograms TP, injected once 48 h prior to testing). Sexually naive, OIL-treated females did not show a preference for males or females, but TP induced a preference for a male. Individual differences in mount frequency were not correlated with preference behavior. In the second experiment, the influence of experience with feminine sexual responses on preference behavior was investigated. OIL-treated and TP-treated females oriented equally toward males and females when they had been given the opportunity to copulate with males prior to the preference tests. The results strongly suggest that prior sexual experience is an important determinant of preference behavior. The female's behavior during sexual interactions was, however, not predictive of later preference.     

Factors affecting the measurement of classically conditioned fear in rats following exposure to escapable versus inescapable signaled shock.

Three experiments are reported in which rats first received 50 escapable or inescapable signaled-shock trials. Experiment 1 (n = 22) employed an acquired-drive paradigm and found inescapable shock subjects learned a hurdle-jump response to escape the signal less rapidly than did escapable-shock subjects. Experiment 2 (n = 24) employed a conditioned emotional response paradigm and found inescapable-shock subjects suppressed more when the signal was introduced in the appetitive bar-pressing task. Both experiments measured spontaneous activity immediately following conditioning and found no group differences. Experiment 3 (n = 39) employed the same activity task and found no difference between escapable- and inescapable-shock groups when the signal was introduced into the activity task. Both groups displayed less activity than a nonshock control group during the signal. The results suggest that lack of control over the shock in the conditioning phase did not result in an increase of conditioned fear. The results are discussed in terms of a learned active-inactive predisposition to respond.     

Studies of instrumental behavior with sexual reinforcement in male rats (Rattus norvegicus): I. Control by brief visual stimuli paired with a receptive female

We describe a novel procedure for measuring instrumental sexual behavior in the male rat by using a second-order schedule of presentation of sexual reinforcement, an estrous female. Experimental assessment and validation of the paradigm have been achieved by examining (a) the importance of the conditioned stimulus in maintaining instrumental responding by measuring the effects of its omission during a test session, (b) the effects and motivational specificity on instrumental behavior of the postejaculatory refractory period (a period of sexual unarousability) and of satiety for food by measuring the impact of each manipulation on animals working for food and for a female, (c) the effects of replacing an estrous female with an anestrous one as the earned reward, and (d) the correlations between conditioned and unconditioned measures of sexual behavior. We conclude that the second-order paradigm provides a means of distinguishing between the effects of neuroendocrine manipulations on incentive motivational and performance variables underlying the expression of sexual behavior.     

Estrogens and progestins enhance spatial learning of intact and ovariectomized rats in the object placement task

Steroid modulation of cognitive function has focused on estrogen (E(2)), but progestins naturally co-vary with E(2) and may also influence cognitive performance. Spatial performance in the object placement task over endogenous hormonal states in which E(2) and progestins vary, and when E(2) and/or progestins were administered, was examined. Experiment 1: Rats in proestrus or estrus had significantly better performance in the object placement task than did diestrus rats. Experiment 2: Rats in the third trimester, post-partum, or lactation exhibited significantly better performance in the object placement task than did rats in the first trimester. Experiment 3: Ovariectomized (ovx) rats administered 17beta-estradiol (0.9 mg/kg), subcutaneously (sc), progesterone (P; 4 mg/kg, sc), or E(2) and P, immediately after training in the object placement task, performed significantly better when tested 4h later, than did control rats administered vehicle (sesame oil 0.2 cc). Experiment 4: ovx rats administered E(2) or P with a 1.5h delay after training in the object placement task, did not perform differently than vehicle-administered controls. Experiment 5: ovx rats administered post-training E(2), which has a high affinity for both E(2) receptor (ER)alpha and beta isoforms, or propyl pyrazole triol (PPT; 0.9 mg/kg, sc), which is more selective for ERalpha than ERbeta, had significantly better performance in the object placement task than did rats administered vehicle or diarylpropionitrile (DPN; 0.9 mg/kg, sc), an ERbeta selective ligand. Experiment 6: ovx rats administered P, or its metabolite, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP; 4 mg/kg, sc), immediately post-training performed significantly better in the object placement task than did vehicle control rats. Thus, performance in the object placement task is better when E(2) and/or P are naturally elevated or when E(2), the ERalpha selective ER modulator PPT, P, or its metabolite, 3alpha,5alpha-THP, are administered post-training.