Claire-Dominique Walker

DISSOCIATION BETWEEN BEHAVIORAL AND HORMONAL RESPONSES TO THE FORCED SWIM STRESS IN LACTATING RATS

Retention of immobility in the Porsolt forced swim test is believed to be dependent upon glucocorticoid secretion in male rats. Because lactating females exhibit increased basal glucocorticoid secretion and blunted stress responses, we tested the hypothesis that lactation‐induced changes in adrenal glucocorticoid and in circulating estrogen and progesterone levels would improve retention and/or acquisition of immobility. Immobility was recorded during 3 intervals of 5 min on day 1 (acquisition) and one 5 min interval 24 h later (retention). Blood samples were collected before the swim test and at various times after the onset of stress for plasma ACTH and corticosterone (B) determinations. Male rats (young = 200 g, old = 325 g) were compared to virgin females (V) and to lactating females in early (day 8‐10, EL) and late (day 17–19, LL) lactation. Adrenalectomy (ADX) and ovariectomy (OVX) were performed 5 and 10 days prior to testing, respectively.

Stress and selective attention: The interplay of mood, cortisol levels, and emotional information processing

The effects of a stressful challenge on the processing of emotional words were examined in college students. Stress induction was achieved using a competitive computer task, where the individual either repeatedly lost or won against a confederate. Mood, attention, and cortisol were recorded during the study. There were four findings: (1) Participants in the negative stressor condition were faster to shift attention away from negative words than positive or neutral words; (2) attentional shifts away from negative words were associated with stress-induced mood lowering; (3) participants in the negative stress condition with elevated scores on the Beck Depression Inventory were slow to disengage attention from all stimuli; and (4) elevated depression scores were associated with lower cortisol change from baseline during the experimental phase, and with higher cortisol levels during the recovery phase. These findings point to information-processing strategies as a means to regulate emotion, and to atypical features of cognitive and adrenocortical function that may serve as putative risk markers of depression.

Kangaroo mother care diminishes pain from heel lance in very preterm neonates: a crossover trial.

BackgroundSkin-to-skin contact, or kangaroo mother care (KMC) has been shown to be efficacious in diminishing pain response to heel lance in full term and moderately preterm neonates. The purpose of this study was to determine if KMC would also be efficacious in very preterm neonates.MethodsPreterm neonates (n = 61) between 28 0/7 and 31 6/7 weeks gestational age in three Level III NICUs in Canada comprised the sample. A single-blind randomized crossover design was employed. In the experimental condition, the infant was held in KMC for 15 minutes prior to and throughout heel lance procedure. In the control condition, the infant was in prone position swaddled in a blanket in the incubator. The primary outcome was the Premature Infant Pain Profile (PIPP), which is comprised of three facial actions, maximum heart rate, minimum oxygen saturation levels from baseline in 30-second blocks from heel lance. The secondary outcome was time to recover, defined as heart rate return to baseline. Continuous video, heart rate and oxygen saturation monitoring were recorded with event markers during the procedure and were subsequently analyzed. Repeated measures analysis-of-variance was employed to generate results.ResultsPIPP scores at 90 seconds post lance were significantly lower in the KMC condition (8.871 (95%CI 7.852–9.889) versus 10.677 (95%CI 9.563–11.792) p < .001) and non-significant mean differences ranging from 1.2 to1.8. favoring KMC condition at 30, 60 and 120 seconds. Time to recovery was significantly shorter, by a minute(123 seconds (95%CI 103–142) versus 193 seconds (95%CI 158–227). Facial actions were highly significantly lower across all points in time reaching a two-fold difference by 120 seconds post-lance and heart rate was significantly lower across the first 90 seconds in the KMC condition.ConclusionVery preterm neonates appear to have endogenous mechanisms elicited through skin-to-skin maternal contact that decrease pain response, but not as powerfully as in older preterm neonates. The shorter recovery time in KMC is clinically important in helping maintain homeostasis.Trial Registration(Current Controlled Trials) ISRCTN63551708

Glucocorticoid rhythms control the rhythm of expression of the clock protein, Period2, in oval nucleus of the bed nucleus of the stria terminalis and central nucleus of the amygdala in rats.

We investigated the involvement of the adrenal glucocorticoid, corticosterone, in the control of the rhythmic expression of the circadian clock protein, Period2, in forebrain nuclei known to be sensitive to glucocorticoids, stressors and drugs of abuse, the oval nucleus of the bed nucleus of the stria terminalis and the central nucleus of the amygdala. We found previously that the daily rhythm of Period2 in these nuclei is uniquely dependent on the integrity of the adrenal glands (Amir S, Lamont EW, Robinson B, Stewart J (2004) A circadian rhythm in the expression of PERIOD2 protein reveals a novel SCN-controlled oscillator in the oval nucleus of the bed nucleus of the stria terminalis. J Neurosci 24:781-790; Lamont EW, Robinson B, Stewart J, Amir S (2005) The central and basolateral nuclei of the amygdala exhibit opposite diurnal rhythms of expression of the clock protein Period2. Proc Natl Acad Sci U S A 102:4180-4184). We now show that, in rats, in the absence of the adrenals, corticosterone replacement via the drinking water, which is associated with daily fluctuations in corticosterone levels, restores the rhythm of Period2 in the oval nucleus of the bed nucleus of the stria terminalis and central nucleus of the amygdala. Corticosterone replacement via constant-release pellets has no effect. These results underscore the importance of circadian glucocorticoid signaling in Period2 rhythms in the oval nucleus of the bed nucleus of the stria terminalis and central nucleus of the amygdala and suggest a novel mechanism whereby stressors, drugs of abuse, and other abnormal states that affect the patterns of circulating glucocorticoids can alter the functional output of these nuclei.

High Neonatal Leptin Exposure Enhances Brain GR Expression and Feedback Efficacy on the Adrenocortical Axis of Developing Rats

Leptin modifies the activity of the hypothalamic-pituitary-adrenal axis in adult rodents and inhibits the production of glucocorticoids from human and rat adrenals in vitro. During development, high levels of circulating leptin and low levels of corticosterone secretion are observed together with adrenal hyporesponsiveness to stress. As chronic neonatal leptin administration reduced stress-induced corticotropin-releasing factor mRNA expression and ACTH secretion in pups, we determined whether elevated leptin levels enhanced the feedback effect of glucocorticoids on the hypothalamic-pituitary-adrenal axis. In naive pups we found a highly significant inverse relationship between plasma levels of leptin and corticosterone (P < 0.01) during postnatal d 6–20. We tested the ability of dexamethasone (1 or 10 μg/kg BW, ip,− 3 h before stress) to suppress ether-induced ACTH secretion in 10-d-old pups that were treated during the neonatal period (d 2–9) with either vehicle or leptin (1 or 3 mg/kg BW, ip, daily). Th...

Increased Fat Intake during Lactation Modifies Hypothalamic-Pituitary-Adrenal Responsiveness in Developing Rat Pups: A Possible Role for Leptin*

High fat feeding reportedly enhances hypothalamus-pituitary-adrenal (HPA) responses to stress in adult rats. The present study tested whether elevated fat intake during suckling could have short and/or long lasting consequences on HPA regulation in the offspring. Mothers were fed either a control (C; 5% fat) or high fat (HF; 20% fat) diet during the last week of gestation and throughout lactation. After weaning (day 21), pups from C and HF mothers were fed a chow diet. Offspring from both C- and HF-fed mothers were tested for ACTH and corticosterone responses to stress on postnatal days 10 and 35. We found that HF feeding produced higher lipid levels in the milk of HF compared with C lactating rat dams and that offspring of these mothers had significantly increased retroperitoneal fat pad weight and relative adipose mass on day 21 as well as elevated plasma leptin levels on days 10 and 21 of age. After weaning, pups from the HF mothers had lower plasma leptin levels than those from C mothers. Maternal dietary fat affected HPA responsiveness in the offspring in an age-related manner. Neonatal pups (day 10) from the HF mothers exhibited a reduction in the ACTH and corticosterone responses to ether stress. However, in 35-day-old offspring from HF-fed dams, stress-induced ACTH secretion was increased compared with that in pups from the C-fed mothers. These results demonstrate that maternal diet and increased fat intake through the milk are important regulators of HPA responsiveness in neonates and prepubertal rats. During neonatal life, the blunted stress responsiveness seen with elevated fat intake and the resulting high leptin levels might protect the pups from excessive HPA activation. After removal of the maternal dietary influence and reduced leptin levels, enhanced ACTH stress responses are observed as in adult rats fed a HF diet. Because of the inverse relationship between plasma levels of leptin and HPA responses in pups, the possibility exists that the effects of the HF diet on stress responsiveness are mediated by changes in leptin exposure during development.

Effect of service dogs on salivary cortisol secretion in autistic children

Children with Autism Syndrome Disorders (ASDs) exhibit social, communicative, and behavioral deficits. We know that human interaction with dogs, which is thought to serve as a social catalyst, results in a decrease of cortisol levels in healthy adults. Introducing service dogs to children with ASD is an attractive idea that has received growing attention in recent decades. However, no study has measured the physiological impact of service dogs on these children. Therefore, the goal of our study was to assess the effects of service dogs on the basal salivary cortisol secretion of children with ASD. We measured the salivary cortisol levels of 42 children with ASD in three experimental conditions; prior to and during the introduction of a service dog to their family, and after a short period during which the dog was removed from their family. We compared average cortisol levels and Cortisol Awakening Response (CAR) before and during the introduction of the dog to the family and after its withdrawal. We found that the introduction of service dogs translated into a statistically significant diminished CAR. Before the introduction of service dogs, we measured a 58% increase in morning cortisol after awakening, which diminished to 10% when service dogs were present. The increase in morning cortisol jumped back to 48% once the dogs were removed from the families (p<0.05). However, service dogs did not have an effect on the childrens average diurnal cortisol levels. These results show that the CAR of children with ASD is sensitive to the presence of service dogs, which lends support to the potential behavioral benefits of service dogs for children with autism.

Chapter 7 Hypothalamic and limbic expression of CRF and vasopressin during lactation: implications for the control of ACTH secretion and stress hyporesponsiveness

Lactation is associated with physiological and behavioral changes that optimize conditions for development of the offspring. Although neuroendocrine and emotional stress responses are blunted, the central mechanisms involved are unclear. In addition to a reduction in stimulatory noradrenergic inputs to paraventricular nucleus (PVN) neurons, we demonstrate that lactation induces: (1) unique phenotypic changes in neuropeptide expression by hypothalamic PVN neurons (reduced expression of corticotropin-releasing factor (CRF) mRNA and increased expression of vasopressin mRNA in parvocellular PVN neurons); and (2) changes in pituitary sensitivity to CRF (reduced) and vasopressin (increased) as a consequence of differential CRF/vasopressin secretion into the hypophysial portal blood. Neurons in the bed nucleus of the stria terminalis (BNST) and the central amygdala (CeA) that are implicated in the control of the hypothalamopituitary-adrenal axis also display changes in lactation: expression of CRF mRNA in the CeA is reduced, consistent with the diminished responsiveness to acoustic startle observed in nursing mothers. In contrast, expression of CRF mRNA is increased in the dorsolateral portion of the BNST, probably because of the tonic increases in endogenous glucocorticoid production during this period. Using immuno-targeted lesions of CRF or vasopressin in the PVN of virgin females, we have shown that CRF neurons of the PVN send inhibitory projections to the dorsolateral portion of the BNST and stimulatory inputs to CRF neurons in the CeA. Thus, it is possible that lactation-induced changes in the activity of parvocellular PVN neurons might also modulate the expression of neuropeptides and neurotransmitters in the BNST and the amygdala.

Reduced Noradrenergic Tone to the Hypothalamic Paraventricular Nucleus Contributes to the Stress Hyporesponsiveness of Lactation

Lactation in mammals is accompanied by a marked decrease in stress responsiveness that we previously attributed, in part, to a reduction in noradrenergic (NA) innervation of hypothalamic paraventricular nucleus (PVN) neurons controlling neuroendocrine stress responses. In the present study, we compared in‐vivo PVN catecholamine secretion by microdialysis between nonlactating and lactating females and tested the effects of NA α–1 and α–2 receptor antagonists (corynanthine and idazoxan, respectively) on the acute stress response of lactating and virgin female rats. To determine if PVN α–adrenoreceptor density, affinity, or synthesis, changes as a function of lactation, we performed receptor autoradiography, Scatchard analysis and in situ hybridization of α–adrenoreceptors. Densitometric analysis of the α–adrenoreceptors in the supraoptic nucleus (SON) was used to evaluate changes in magnocellular neurons. Endogenous PVN norepinephrine release under basal conditions was lower in lactating females than in females who had their pups removed for 2 days, and microdialysate concentrations of adrenaline and MHPG were attenuated in lactating females. α–2 adrenoreceptor density in the PVN showed a significant decrease from lactation day 3 to lactation days 10–12 and a reduction to 40% of virgin controls on days 10–20 of lactation. A similar pattern was observed for the SON. The affinity of hypothalamic α–2 adrenoreceptors was reduced as a function of lactation. α–1 adrenoreceptor density in the PVN and in the hypothalamus rose as a function of lactation, although the affinity of these receptors was not altered. In contrast, α–1D adrenoreceptor subtype mRNA expression in the PVN decreased in middle lactating females (day 10) compared to virgins. Intracerebroventricular (icv) application of idazoxan, significantly increased the ACTH response to swim stress in virgin females, but had the opposite effect in lactating females. In contrast, icv corynanthine treatment significantly decreased the ACTH response in virgins, but not in lactating females. Overall, these data suggest that the secretion of NA in the PVN is reduced during lactation, and that the ability of PVN parvocellular neurons to respond to changes in synaptic NA levels (i.e. after stress) is also altered.

Maternal high-fat intake alters presynaptic regulation of dopamine in the nucleus accumbens and increases motivation for fat rewards in the offspring.

High caloric intake during early postnatal development can have long term consequences for the offspring. We previously reported that the adult offspring of dams fed a high-fat diet during the last week of gestation and throughout lactation display blunted locomotor response to amphetamine (AMP) and reduced sensitization to the drug compared to offspring of control diet dams. Here, we report that the subsensitivity of high-fat offspring to AMPs locomotor stimulant action reflects, at least in part, altered regulation of nucleus accumbens (NAc) dopamine (DA) transmission. When compared to controls, the DA response of high-fat animals to AMP, as measured with microdialysis, was attenuated in the NAc, but unaffected in the prefrontal cortex (PFC). A relatively higher activity of NAc synaptosomal DA transporter sites without changes in vesicular monoamine transporter (VMAT) uptake capacity was also observed in high-fat offspring. Moreover, ventral tegmental area (VTA) D(2) receptor mRNA levels were decreased in high-fat offspring, suggesting a reduction in DA release-regulating D(2) autoreceptors in terminal regions such as the NAc. The magnitude of locomotor response to D(2/3) receptor activation (with quinpirole) was greater in high-fat than in control animals despite having comparable postsynaptic D(2) mRNA levels in the NAc. Finally, while operant responding for a sugar-enriched food reward did not differ between diet groups, high-fat offspring displayed increased operant responding for a fat-enriched reward compared to controls. These findings add to mounting evidence that early life exposure to elevated dietary maternal fat can lead to long lasting changes in DA-mediated behavioral responses to stimulant drugs and fat-enriched foods.