Neonatal handling increases cardiovascular reactivity to contextual fear conditioning in borderline hypertensive rats (BHR)

Much research has demonstrated that events occurring in early life can have a profound influence on future biobehavioral responses to stressful and emotion provoking situations. The purpose of these studies was to determine the effects of an early environmental manipulation, handling (HAN) on cardiovascular (CV) reactivity, freezing behavior and corticosterone (CORT) responses to contextual fear conditioning in the borderline hypertensive rat (BHR),which is susceptible to environmental stressors. HAN subjects were separated from the nest for 15 min/day on post-natal days 1-14, while non-handled (NON-HAN) controls remained in the home cage. Adult subjects were exposed to the contextual fear conditioning procedure and returned to the chamber 24 h later for a 10 min test period. HAN subjects displayed significantly more freezing behavior compared to NON-HAN(92%+/-2.2 vs 80.7%+/-5.7, p<.05). Although resting MAP did not differ between groups, HAN subjects had increased MAP reactivity when re-exposed to the chamber. In addition, HAN subjects had significantly lower CORT levels at the end of the 10 min test period (174.2+/-9 ng/ml vs 237.2+/-12.9 ng/ml, p<.05). In the second experiment, CORT responses to 60 min of restraint stress and recovery following return to the home cage were assessed in separate groups of HAN and NON-HAN subjects. HAN subjects showed reduced CORT levels in response to acute restraint stress. These results indicate that neonatal handling can modulate biobehavioral responses to contextual fear conditioning in BHR and may suggest a useful model with which to study emotionality and susceptibility to CV disease.     

Prepartal chronic stress increases anxiety and decreases aggression in lactating female mice.

The effects of two types of prepartal chronic stress on maternal behavior, anxiety, and maternal aggression during lactation were assessed in female outbred Swiss mice. Two groups (n = 18 each) were subjected to 10 consecutive daily sessions of restraint stress (RS) or novel environment stress (NES) from Day 4 to Day 14 of pregnancy. A third group (n = 18) was left undisturbed during pregnancy (controls, C group). All females underwent a maternal behavior test (10-min observation after separation and reunion with the pups) on Postpartum Day (PD) 1, an anxiety test (a light-dark conflict test) on PD 6, and a maternal aggression test (5-min exposure to an unfamiliar adult male) on PD 7. NES and RS groups tended to show higher amounts of maternal care. Anxiety increased in the stressed females compared with controls, whereas the opposite was true for maternal aggression. In the RS group, anxiety was negatively correlated with maternal aggression. These results suggest that chronic stress may have produced neuronal and endocrine alterations in the dams, which may have led to increased avoidance of aversive stimuli. The results also support the hypothesis that, in lactating mice, anxiety is inversely related to the probability of displaying intense forms of aggression.     

Neonatal handling alters feeding behavior of adult rats

Stress during the neonatal period leads to a large number of behavioral and biochemical alterations in adult life. The aim of this study is to verify the effects of handling and tactile stimulation during the first 10 days of life on feeding behavior in adult rats. Litters were divided into (1) intact; (2) handled (10 min/day); and (3) handled and tactile stimulated (10 min/day). Procedures were performed on Days 1–10 after birth. When adults, rats were tested for ingestion of sweet and savory snacks. We also measured body weight, ingestion of standard lab chow, and consumption of water and 1% glucose and 1.5% NaCl solutions. Stressed rats (handling and handling+tactile stimulation groups) consumed more sweet (two-way ANOVA, P=.008) or savory snacks (P=.001) than intact ones. This effect was observed in males and females. There were no differences in body weight, ingestion of standard lab chow, water, or in the ingestion of sweetened or salty solutions between groups. The same animals were tested later in life (15 months of age), and the effect was still evident. We suggest that handling during the neonatal period leads to alterations in the CNS of rats, causing an increased ingestion of palatable food in adult life, and this alteration probably persists throughout the whole life.     

Ovariectomy does not attenuate aggression by primiparous lactating female rats.

Nulliparous female hooded rats were allowed to cohabit with a sexually active male in a large living cage. Aggression toward an unfamiliar female was assessed during the second and third week of pregnancy. Within 12 to 24 h following parturition females were ovariectomized (n = 7) or sham-ovariectomized (n = 6) in a manner that balanced previous aggression scores. Aggression was assessed at 48 h following ovariectomy and at three weekly intervals thereafter. Ovariectomized and sham-ovariectomized females did not differ in the number of attacks, number of bites, duration of on-top, or frequency of piloerection on any test day following parturition. These results indicate that circulating levels of ovarian steroids do not influence the level of aggression by a primiparous lactating female toward an unfamiliar female conspecific.     

Neonatal handling reverses behavioral abnormalities induced in rats by prenatal stress

The aim of this study was to see whether neonatal handling can reverse the behavioral deficits induced in rats by unpredictable prenatal stress. Rats (24) were exposed to random noise and light stress (RS) on a random basis throughout pregnancy. Half the litters of RS and control (C) dams were subjected to neonatal handling (NH), 3' daily for 21 days. Behavioral measures, open field in both sexes and plus maze test in females only were conducted at 1.5-2 months, and spatial lateralization by amphetamine-induced rotation, in females at 3 months. RS caused significant increases in emotionality and timidity (higher incidence of defecation and less time in open arms of plus maze), and a change in directional bias towards the left. NH completely reversed all these behavioral abnormalities in RS rats but had little effect in C. It is concluded that NH can influence postnatal development of brain organisation in the opposite direction to that induced by prenatal stress.     

Reproducible increases in intramammary pressure after spinal cord stimulation in lactating rats

Summary Intramammary pressure was recorded in anaesthetized lactating rats during electrical stimulation of the anterolateral pathways in the T12/L1 region of the spinal cord. In 18 rats, electrical stimulation at 10 Hz or more for 10–30 s caused a reproducible increase in intramammary pressure. The mammary gland responses were similar to those resulting from stimulation of the neurohypophysis with the same parameters, and were eliminated after complete destruction of the neural stalk; they were not associated with any consistent change in blood pressure. In 3 rats, a mammary gland response to spinal cord stimulation was obtained only after administration of the -adrenergic blocker, propranolol, which facilitates suckling-induced reflex milk-ejections. These results suggest that spinal cord stimulation can cause the release of oxytocin; the functional significance of such a release is discussed in relation to the milk-ejection reflex.Supported by a fellowship from INSERM     

Parachlorophenylalanine-induced serotonin depletion increases offensive but not defensive aggression in male rats

Cerebral 5-HT depletion has been shown to facilitate elicitation of various kinds of aggressive behavior in rats. The question as to whether both offensive and defensive aggressive reactions are affected to the same extent was examined in a resident-intruder paradigm where an ethological analysis of the two animals allows an evaluation of non-social activities as well as agonistic interactions, including both offense and defense. PCPA (375 mg/kg IP) was administered either to the resident or the intruder and the interactions with an untreated conspecific were recorded in the resident's home cage for an 8 min period three days after injection when 5-HT was maximally reduced. PCPA treatment increased the occurrence of social approach and offensive postures in resident rats, whereas their untreated partners displayed more defensive reactions. When intruders were injected, only non-significant increases in approach and offense were observed. In no case did PCPA affect occurrence of defensive postures in the injected animals. These results confirm that serotonin plays a role in controlling offensive aggression but not defensive behavior.     

Neonatal handling reduces the number of cells in the locus coeruleus of rats

Neonatal handling induces long-lasting effects on behaviors and stress responses. The objective of the present study was to analyze the effects of neonatal handling (from the 1st to the 10th day after delivery) on the number of cells and volume of locus coeruleus (LC) nucleus in male and female rats at 4 different ages: 11, 26, 35, and 90 days. Results showed significant reductions in the number of cells and the volume of the LC nucleus in neonatally handled males and females compared with nonhandled rats. Environmental stimulation early in life induced a stable structural change in a central noradrenergic nucleus, which could be one of the causal factors for the behavioral and hormonal alterations observed in adulthood.     

Early exposure to methylphenidate increases fear responses in an aversive context in adult rats

The effects of methylphenidate hydrochloride (MPH) administration during development on fear acquisition and retention in adulthood were examined using classical fear conditioning. Male Sprague-Dawley rats were administered MPH (2 mg/kg) or saline twice daily from postnatal day (PD) 25 to 39, and were trained and tested on PD 81 and 82. During training, shock unconditioned stimulus (US) presentations were explicitly paired with an auditory conditioned stimulus (CS) or occurred unsignaled in the training context. No effect of MPH treatment was found during fear acquisition when shock was signaled or unsignaled during training, but 24 h retention tests in the training context revealed enhanced fear responses in MPH-treated animals that received unsignaled training. These results support recent reports of enhanced anxiety-like behaviors in adult rats caused by early developmental MPH treatment and highlight the need for further research into the long-term effects of developmental exposure to stimulants aimed at pediatric populations.     

Olfactory control of aggression in lactating female housemice.

Wild female lactating mice were tested for aggression toward strange wild male mice doused with either the test female's own urine (Owns), the urine of other wild females (Novels), or water (Controls). Treatment effects were assessed against an aggression index comprised of 5 different behaviors shown to be related by a factor analysis. Females aggressed more toward Novel-scented opponents than toward either Owns or Controls, the latter 2 conditions failing to differ statistically. It was concluded that an olfactorily-mediated mechanism controls the recognition of intruders by aggressive lactating housemice.     

Role of maternal behavior on aggression,fear and anxiety

Concomitant to the expression of maternal behavior, the lactating female develops anxiolysis in the elevated plus maze test, aggression towards intruders and reduced fear in response to a sudden auditory stimulus. This study aims to determine if these behavioral changes are associated with maternal behavior independently of the endocrine status that characterizes gestation, parturition and lactation. To assess this purpose, the behavior of lactating females was compared to that exhibited by maternal and nonmaternal ovariectomized rats untreated with steroid hormones. In contrast with lactating dams, sensitized animals (rats that displayed maternal behavior after a continuous contact with young pups) did not display reduced anxiety in the plus maze test. However, the sensitized females showed behaviors characteristic of lactating rats, such as some components of maternal aggression and reduced fear, though much less intensely than dams. These results suggest that aggression and reduced fear, but not anxiolysis, partially depend on the development of maternal behavior.     

Predatory aggression and irritable aggression: shock-induced fighting in mouse-killing rats

Two experiments were conducted to assess shock-induced aggressive behavior in mouse-killing and nonkilling rats. The purpose of this research was to determine whether the different types of aggressive behavior covary, or whether they are unrelated. At both 2-mA and 1-mA shock intensities the killing and nonkilling rats did not differ with respect to shock-induced fighting.     

Neonatal maternal separation in male rats increases intestinal permeability and affects behavior after chronic social stress

Prolonged maternal separation in rats has several effects on health and behavior. Here we investigated how maternal separation might interact with social stress in adulthood on behavior and gastrointenstinal permeability. The effects of either daily 180 min long term pup-dam separation (LMS) during the stress hyporesponsive period or daily 10 min brief maternal separation (BMS) on behavior, corticosterone and intestinal permeability were investigated, compared to a non-handling (NH) condition in male offspring. The animals from each separation condition were then randomly assigned to adult stress and control conditions, where the stress condition was exposure to 14 days of social instability (CSI). Sucrose preference, elevated plus maze behavior and corticosterone were measured. Colitis was experimentally induced by dextran sulfate sodium for 7 days, followed by measurement of intestinal permeability using the (51)CrEDTA method. Granulocyte marker protein was measured in feces and colons were examined histologically for inflammation. Prior to the social stress, the LMS offspring showed elevated corticosterone levels, lower elevated plus maze activity and less fluid consumption. After social stress, corticosterone levels were suppressed in LMS animals and again they showed less fluid consumption. LMS animals had significantly higher intestinal permeability, but only when also exposed to the social stress in adulthood. The current results support a two-hit model, whereby early life events interact with adult life events in altering animals' vulnerability.     

Sodium appetite in lactating rats

Lactating rats that were given free access to sodium-deficient food, water, and 0.51 M NaCl solution showed no evidence of sodium appetite. The estimated daily loss of 1-2 mEq Na in milk was replaced by basal daily intake of 2-5 ml of saline. Sodium loss in urine was minimal, but milk sodium concentration was unchanged, and pups grew normally. Saline intake was enhanced when lactating rats that had been maintained on standard laboratory chow were injected with 30% polyethylene glycol solution to reduce plasma volume but no more so than when virgin female rats or male rats were similarly colloid-treated. Lactating rats markedly increased their intake of NaCl solution after simply depriving them of dietary sodium for 4 days, whereas male and virgin female rats did not. These findings indicate that pronounced sodium appetite does not invariably accompany lactation in rats, although it can occur whenever such animals become hypovolemic or sodium deficient.     

Neonatal maternal separation in male rats increases intestinal permeability and affects behavior after chronic social stress

Prolonged maternal separation in rats has several effects on health and behavior. Here we investigated how maternal separation might interact with social stress in adulthood on behavior and gastrointenstinal permeability. The effects of either daily 180 min long term pup-dam separation (LMS) during the stress hyporesponsive period or daily 10 min brief maternal separation (BMS) on behavior, corticosterone and intestinal permeability were investigated, compared to a non-handling (NH) condition in male offspring. The animals from each separation condition were then randomly assigned to adult stress and control conditions, where the stress condition was exposure to 14 days of social instability (CSI). Sucrose preference, elevated plus maze behavior and corticosterone were measured. Colitis was experimentally induced by dextran sulfate sodium for 7 days, followed by measurement of intestinal permeability using the ⁵¹CrEDTA method. Granulocyte marker protein was measured in feces and colons were examined histologically for inflammation. Prior to the social stress, the LMS offspring showed elevated corticosterone levels, lower elevated plus maze activity and less fluid consumption. After social stress, corticosterone levels were suppressed in LMS animals and again they showed less fluid consumption. LMS animals had significantly higher intestinal permeability, but only when also exposed to the social stress in adulthood. The current results support a two-hit model, whereby early life events interact with adult life events in altering animals' vulnerability.     

Skin conductance fear conditioning impairments and aggression: A longitudinal study

Autonomic fear conditioning deficits have been linked to child aggression and adult criminal behavior. However, it is unknown if fear conditioning deficits are specific to certain subtypes of aggression, and longitudinal research is rare. In the current study, reactive and proactive aggression were assessed in a sample of males and females when aged 10, 12, 15, and 18 years old. Skin conductance fear conditioning data were collected when they were 18 years old. Individuals who were persistently high on proactive aggression measures had significantly poorer conditioned responses at 18 years old when compared to others. This association was not found for reactive aggression. Consistent with prior literature, findings suggest that persistent antisocial individuals have unique neurobiological characteristics and that poor autonomic fear conditioning is associated with the presence of increased instrumental aggressive behavior.     

Sleep deprivation increases threat beliefs in human fear conditioning

Sleep disturbances and anxiety disorders exhibit high comorbidity levels, but it remains unclear whether sleep problems are causes or consequences of increased anxiety. To experimentally probe the aetiological role of sleep disturbances in anxiety, we investigated in healthy participants how total sleep deprivation influences fear expression in a conditioning paradigm. In a fear conditioning procedure, one face stimulus (conditioned stimulus [CS+]) was paired with electric shock, whereas another face stimulus was not (unpaired stimulus [CS?]). Fear expression was tested the next morning using the two face stimuli from the training phase and a generalization stimulus (i.e. a morph between the CS+ and CS? stimuli). Between fear conditioning and test, participants were either kept awake in the laboratory for 12 hr (n = 20) or had a night of sleep at home (n = 20). Irrespective of stimulus type, subjective threat expectancies, but not skin conductance responses, were enhanced after sleep deprivation, relative to regular sleep. These results suggest that sleep disturbances may play a role in anxiety disorders by increasing perceived threat.