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)     

Steady-state methadone effect on generalized arousal in male and female mice.

Methadone is widely used in treatment of short-acting opiate addiction. The on-off effects of opioids have been documented to have profound differences from steady-state opioids. The authors hypothesize that opioids play important roles in either generalized arousal (GA) or aversive state of arousal during opioid withdrawal. Both male and female C57BL6 mice received steady-state methadone (SSM) through osmotic pumps at 10 or 20 mg/kg/day, and GA was measured in voluntary motor activity, sensory responsivity, and contextual fear conditioning. SSM did not have any effect on those GA behaviors in either sex. Females had higher activity and less fear conditioning than males. The effects of SSM on stress-responsive orexin gene expression in the lateral hypothalamus (LH) and medial hypothalamus (MH, including perifornical and dorsomedial areas) were measured after the behavioral tests. Females showed significantly lower basal LH (but not MH) orexin mRNA levels than males. A panel of GA stressors increased LH orexin mRNA levels in females only; these increases were blunted by SSM at 20 mg/kg. In summary, SSM had no effect on GA behaviors. In females, SSM blunted the GA stress-induced LH orexin gene expression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Stress enhances excitatory trace eyeblink conditioning and opposes acquisition of inhibitory conditioning

Exposure to a brief, stressful event is reported to facilitate classical eyeblink conditioning in the male rat (Rattus norvegicus) by use of a delay paradigm in which the conditioned stimulus (CS) and unconditioned stimulus (US) overlap and coterminate. This study examined the effects of stress on trace conditioning, a task in which the CS and US were separated by 500 ms. Experiment 1 showed that exposure to brief (1 s), low-intensity (1 mA) tailshocks facilitated acquisition 24 hr later. Experiment 2 showed that stressor exposure did not affect retention or extinction of trace conditioning in rats that were stressed after acquisition. Experiment 3 showed that exposure to the same stressor opposed acquisition of inhibitory conditioning. These results suggest that exposure to a stressful event persistently facilitates acquisition of trace conditioning and enhances a bias toward acquiring positive versus negative associations.     

Effects of chronic morphine treatment on responding for intracranial stimulation in female versus male rats.

Morphine was administered to Sprague-Dawley rats twice daily at 0, 3, 10, and 20 mg/kg injection during Weeks 1, 2, 3, and 4, respectively; responding for medial forebrain bundle stimulation was assessed 1, 2, and 3 hr after morning injections in female versus male rats. There were no sex differences in responding under control conditions (Week 1). Morphine's effect on response rate depended on dose, time post-injection, stimulation frequency, and day of treatment. Significant sex differences in morphine's effects occurred at 10 mg/kg, which decreased responding more in males at 1 hr and increased responding more in females at 2 hr, at some frequencies and on some test days. Similar trends were observed at other frequencies, test days, and doses. Morphine's differential effect in males versus females in this procedure suggests that sex comparisons of opioid effects in many animal models may be influenced by sex difference in opioid effects on behavior output. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Social malleability in cowbirds: New measures reveal new evidence of plasticity in the eastern subspecies (Molothrus ater ater).

The social experiences of young Molothrus ater ater cowbirds were manipulated in a 2-year study. In the 1st year, males were housed with pairs of canaries. The males were tested in 3 social contexts. Also, vocal repertoires were recorded and played back to females. In contrast to a previous study of the M. a. artemisiae subspecies, the males did not vocalize to the canaries in courtship tests (T. M. Freeberg, A. P. King, & M. J. West, 1995) but showed incompetent courtship of female cowbirds. In their 2nd year, half of the males were housed with older males and female cowbirds, and half were housed with only females. Those exposed to older males courted much more successfully than did those deprived of such experience. All males developed new repertoires, and song potencies did not correlate across years. The data reveal intraspecific variation in the ontogeny of mate recognition but intraspecifc dependence on social learning to acquire courtship skills. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Corneal manifestations of metabolic diseases

The extent to which sex differences in the behavioral effects of frontal injury in the adult rat can be attributed to differential exposure to testosterone (T) during development was investigated. The effects of these factors on brain weight and relative brain size were also examined. At birth, males were gonadectomized (GDX) or not and females were given T or oil injections. In adulthood, all animals were GDX or sham-operated and received either bilateral aspiration lesions of the medial frontal cortex or a sham operation. Rats were tested on the Morris water maze task, the radial arm maze (RAM), and the landmark water task. The effects of frontal injury on performance of the Morris water maze task were greater in rats not exposed to T at birth, there was no effect of neonatal T exposure on performance on the RAM, and on the landmark water task there was a complicated interaction of sex and neonatal T exposure in rats with frontal injury.     

The bed nucleus of the stria terminalis is critically involved in enhancing associative learning after stressful experience.

Exposure to an acute stressful event enhances trace eyeblink conditioning in male rats, even when rats begin training days after the stressor (Shors, 2001). The authors examined whether the bed nucleus of the stria terminalis (BNST), an area involved in stress and anxiety, is critically involved in this effect and, if so, when. The authors found that excitotoxic lesions to the BNST prevented the enhanced conditioning after stressor exposure. In addition, temporary inactivation of the BNST during the stressor did not alter enhanced responding, whereas inactivation during training prevented the enhancement. These data indicate that stressful experience induces persistent changes in the BNST that are necessary for enhancing learning well after the stressful event has ceased. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Female-enhanced aggression in male rats: Effects of genital anesthesia, castration, or preoptic lesions.

Male rats that had cohabited with ovariectomized females for 2 weeks became more aggressive toward male intruders after a novel estrous female had been placed in their home cages for a period of 4 hr on the previous day. No increase in aggression was seen in males exposed to anestrous females. Genital anesthesia did not attenuate the female-enhanced aggression effect. By contrast, no enhancement of aggression was observed in long-term castrated males after 24 hr of exposure to estrous females. Rats with bilateral electrolytic lesions in the medial preoptic area showed a normal female-enhanced aggression effect. The observations that exposure to females facilitates aggression in males subjected to genital anesthesia and in males with preoptic lesions raise the possibility that copulatory cues are not always required for the effect. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sex differences in the effects of frontal cortex injury: Role of differential hormonal experience in early development.

The extent to which sex differences in the behavioral effects of frontal injury in the adult rat can be attributed to differential exposure to testosterone (T) during development was investigated. The effects of these factors on brain weight and relative brain size were also examined. At birth, males were gonadectomized (GDX) or not and females were given T or oil injections. In adulthood, all animals were GDX or sham-operated and received either bilateral aspiration lesions of the medial frontal cortex or a sham operation. Rats were tested on the Morris water maze task, the radial arm maze (RAM), and the landmark water task. The effects of frontal injury on performance of the Morris water maze task were greater in rats not exposed to T at birth, there was no effect of neonatal T exposure on performance on the RAM, and on the landmark water task there was a complicated interaction of sex and neonatal T exposure in rats with frontal injury. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neurochemical basis of conditioned partner preference in the female rat: II. Disruption by flupenthixol.

The effects of the dopamine receptor antagonist flupenthixol were examined on the development of conditioned partner preference induced by paced copulation in female rats. In Experiment 1, ovariectomized, hormone-primed rats were conditioned to associate scented and unscented males with paced and nonpaced copulation, respectively. Females in Experiment 2 associated albino or pigmented males with paced or nonpaced copulation. Flupenthixol or saline was administered before each conditioning trial. During a final drug-free preference test, females could choose to copulate with either a pacing-related or nonpacing-related male. Saline-trained females copulated preferentially with the pacing-related male, whereas flupenthixol disrupted odor but not strain conditioning. The role of dopamine in conditioned partner preference depends on the type of stimuli to be learned. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Gender- and age-dependent differences in latent inhibition following pre-weaning non-handling: implications for a neurodevelopmental animal model of schizophrenia

Latent inhibition (LI) refers to retarded conditioning to a stimulus as a consequence of its prior nonreinforced pre-exposure, and is considered to index the capacity of an organism to ignore irrelevant stimuli. LI disruption has received increasing attention as an animal model of the widely described attentional deficit of schizophrenia, consisting of an inability to ignore irrelevant stimuli. The present experiments investigated the effects of infantile manipulations on the development of LI. Male and female rats handled or nonhandled in infancy (days 1-22), were tested at 3 and 16 months. Young handled animals had lower emotional reactivity than nonhandled, and this difference persisted in females at 16 months. At 3 months. LI, poorer conditioning of stimulus pre-exposed as compared to nonpre-exposed rats, was obtained in handled and nonhandled females, as well as in handled males, but was absent in nonhandled males. This pattern changed at 16 months: both nonhandled males and females failed to show LI. These gender- and age-dependent effects of pre-weaning manipulations on LI loss may provide an animal parallel to the susceptibility of young adult males to schizophrenia and the attenuation of gender differences in long-term outcome schizophrenia.     

The loss of latent inhibition across compound conditioning.

Six experiments used a magazine approach paradigm with rats to investigate latent inhibition (LI). Experiment 1 found that compound conditioning did not increase evidence for LI, in contrast to predictions from acquisition-deficit models that are based on a common error term (e.g., J. M. Pearce & G. Hall, 1980; A. R. Wagner, 1981). Instead, it appeared that preexposed and non-preexposed stimuli conditioned to the same asymptote following compound conditioning, as is the case when these stimuli are conditioned separately. This was confirmed in three further experiments that used probe trials to measure conditioning to each conditioned stimulus across the course of compound training. In these experiments, LI was observed during initial but not extended compound training, consistent with predictions derived from M. E. Bouton (1997) and the SLG model (N. A. Schmajuk, Y. Lam, & J. A. Gray, 1996). However, 2 further experiments did not support these models. Instead, these findings are most consistent with models that use separate error terms to compute the associative strength of conditioned stimuli conditioned in compound (S. E. Brandon, E. H. Vogel, & A. R. Wagner, 2003; M. E. Le Pelley, 2004; N. J. Mackintosh, 1975). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioned stimulus control in the rat circadian system depends on clock resetting during conditioning.

The authors examined the ability of a conditioned stimulus (CS; mild air disturbance) previously paired with an entraining light pulse to reset the circadian pacemaker in rats. Rats were entrained to a single 30-min light stimulus delivered every 25 hr or 24 hr (T cycle). Each daily light presentation was paired with the CS. After at least 20 days of stable entrainment to each of the T cycles, the rats were allowed to free run and were then presented with the CS at circadian time 15. CS-induced phase shifts in wheel-running activity rhythms were taken as evidence for conditioning. For the most part, conditioning occurred after CS-light pairings on the 25-hr but not 24-hr T cycle. The results suggest that CS control of the circadian clock phase depends on the effect that the entraining light pulse has on the clock during conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Proliferation of granule cell precursors in the dentate gyrus of adult monkeys is diminished by stress

Although granule cells continue to be added to the dentate gyrus of adult rats and tree shrews, this phenomenon has not been demonstrated in the dentate gyrus of adult primates. To determine whether neurons are produced in the dentate gyrus of adult primates, adult marmoset monkeys (Callithrix jacchus) were injected with BrdU and perfused 2 hr or 3 weeks later. BrdU is a thymidine analog that is incorporated into proliferating cells during S phase. A substantial number of cells in the dentate gyrus of adult monkeys incorporated BrdU and approximately 80% of these cells had morphological characteristics of granule neurons and expressed a neuronal marker by the 3-week time point. Previous studies suggest that the proliferation of granule cell precursors in the adult dentate gyrus can be inhibited by stress in rats and tree shrews. To test whether an aversive experience has a similar effect on cell proliferation in the primate brain, adult marmoset monkeys were exposed to a resident-intruder model of stress. After 1 hr in this condition, the intruder monkeys were injected with BrdU and perfused 2 hr later. The number of proliferating cells in the dentate gyrus of the intruder monkeys was compared with that of unstressed control monkeys. We found that a single exposure to this stressful experience resulted in a significant reduction in the number of these proliferating cells. Our results suggest that neurons are produced in the dentate gyrus of adult monkeys and that the rate of precursor cell proliferation can be affected by a stressful experience.     

Comparison of the effects of early handling and early deprivation on conditioned stimulus, context, and spatial learning and memory in adult rats.

Effects of manipulations of the rat pup-dam relationship on affective learning and memory in adulthood have received scant systematic investigation. The authors previously described how early handling (EH; 15 min isolation/day) and early deprivation (ED; 4 hr isolation/day) exert similar effects on spontaneous adult affect (open-field behavior, acoustic startle, endocrine stress response) relative to nonhandling (NH; C. R. Pryce, D. Bettschen, N. I. Bahr, & J. Feldon, 2001). The present study demonstrates that both EH and ED adults exhibit enhanced active avoidance relative to NH adults. Fear-conditioned context and conditioned stimulus (CS) freezing were unaffected in both EH and ED, but stress hormone responses to the CS were reduced in EH males and ED females relative to NH. In the water maze, ED adults exhibited enhanced spatial learning and memory relative to NH. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Polyandrous females discriminate against previous mates

In most animal species, particularly those in which females engage in polyandry, mate choice is a sequential process in which a female must choose to mate or not to mate with each male encountered. Although a number of theoretical and empirical investigations have examined the effects of sequential mate choice on the operation of sexual selection, how females respond to solicitation by previous mates has received little attention. Here, we report the results of a study carried out on the polyandrous pseudoscorpion, Cordylochernes scorpioides, that assessed the sexual receptivity of once-mated females presented after a lapse of 1.5 hr or 48 hr with either their first mate or a different male. Females exhibited a high level of receptivity to new males, irrespective of intermating interval. By contrast, time between matings exerted a strong effect on female receptivity to previous mates. After a lapse of 48 hr, females did not differ significantly in their receptivity toward previous mates and different males, whereas at 1.5 hr after first mating, females were almost invariably unreceptive to males from whom they had previously accepted sperm. This result could not be attributed to male size or mating experience or to male sexual receptivity. Indeed, males were as willing to transfer sperm to a previous mate as they were to a new female. This difference between males and females in their propensity to remate with the same individual may reflect a conflict between the sexes, with males seeking to minimize postcopulatory sexual selection and females actively keeping open the opportunity for sperm competition and female choice of sperm by discriminating against previous mates.     

Postconditioning isolation disrupts contextual conditioning: an experimental analysis

Contextual-fear conditioning requires a lengthy retention period to fully emerge. This phenomenon might reflect the consolidation of a representation of the context that can be used to evoke fear. To investigate this hypothesis, 25 day-old rats that were returned to their home cages after conditioning were compared with rats that were isolated in a novel room. Isolation disrupted contextual but not auditory-cue fear conditioning when the conditioning-isolation interval was 2 hr or less, but not when it was 24 hr. Preexposure to the context prevented the isolation effect, and isolation disrupted this effect of context preexposure. These results support the consolidation hypothesis and the view that contextual- and auditory-cue fear conditioning depend on different processes.     

A comparison of contextual and generalized auditory-cue fear conditioning: evidence for similar memory processes

A number of variables influence contextual, but not auditory-cue, fear conditioning. However, several of these variables (isolation, stimulus preexposure, retention interval, and age) affect generalized auditory-cue fear. More generalized fear was found when (a) rats were isolated in a novel environment than when returned to their home cages, (b) the retention interval was 3 hr rather than 24 hr, and (c) in 18-day-old compared with 25-day-old rats. Moreover, preexposure to the auditory cue eliminated the isolation effect. At a behavioral-psychological level, these variables may exert their effects by influencing the processes that construct a memory representation of the stimulus. At a neural systems level, they may influence processing carried out in the thalamo-corticoamygdaloid auditory pathway.     

Age and gender influence basal and stress-modulated hypothalamic-pituitary-thyroidal function in Fischer 344/N rats

To investigate possible gender- and age-associated changes of the hypothalamic-pituitary-thyroid (HPT) axis at baseline and during stress, we studied healthy young (3-month) and old (23-month) female 344/N Fischer rats at the basal state and after 2 h of immobilization (IMMO), in parallel to age-matched male rats. At baseline, there were no major differences on HPT axis functions between young female and male animals. Old age was associated with impaired central thyroid function in both genders, albeit to a much lesser extent in females than in males. Plasma prolactin (PRL) levels were similar in young females and males but were higher in old females than males. IMMO inhibited HPT axis functions in both genders in young, but not old animals. Thus, plasma TSH and hypothalamic TRH mRNA levels were decreased by IMMO in young, but not in old rats of both genders. IMMO increased plasma PRL in young and old males, but did not have any effect in young and old females. In summary, these data indicate that age and gender exert diverse effects on HPT axis functions at baseline and after stress.     

Effects of chronic systemic administration of 5-HT on food intake and body weight in rats

The effects of chronic peripheral administration of 5-HT on food intake and body weight was investigated. In normal male Wistar rats, normal female Wistars, obese Zucker males, ovariectomised Wistar females, or normal Wistar males free fed a cafeteria diet, suppression of the creeping weight gain typical of control animals is observed. In females, this effect is not dependent on the local hormonal environment, because intact and ovariectomised females showed similar responses to treatment. One sex difference is that the weight suppressive effect in males is accompanied by an anorectic effect, whereas this anorectic effect is absent in females. Thus, although reduced food intake may partially explain the suppression of weight gain in males, in females it must be due to other, perhaps metabolic, effects. It is possible that these metabolic effects may also occur in males, suggesting one possible explanation of why the effect was typically larger in males than females.