Long-term effects of fetal ethanol exposure on pituitary-adrenal response to stress

Pregnant female rats were fed either a 5.0–5.5% w/v ethanol-containing liquid diet ad lib or pair-fed the isocaloric control diet during gestation weeks 2 and 3. At 75–105 days of age, female offspring of the ethanol-treated dams showed significantly greater corticosterone responses than pair-fed- or normally-derived offspring to the stress of cardiac puncture or of noise and shaking, while pituitary-adrenal responses to exposure to a novel environment, cold or 2–3 days of fasting were normal. Adrenal sensitivity to ACTH in dexamethasone-suppressed adult offspring was unaffected by the prenatal treatment. The results demonstrate that fetal ethanol exposure enhances adult pituitary-adrenal responses to certain stressors, including alcohol as demonstrated previously, and suggest that the long-term effects may be mediated by developmental actions of alcohol on central neural mechanisms involved in the regulation of this neuroendocrine system.     

Effects of naloxone on corticosterone response to stress

The effect of naloxone on the corticosterone response to restraint stress was examined. Naloxone (8 mg/kg, IP) did not alter basal corticosterone or the magnitude of the corticosterone response to restraint stress. Naloxone did, however, retard the fall in corticosterone following the end of restraint stress; thus the drug prolonged the stress response. These data suggest that endogenous opiates play a role in the restoration of corticosterone levels back to normal after stress.     

The effects of perinatal AZT exposure on the acoustic startle response in adult rats

AZT (azidothymidine, zidovudine, ZDV) has become the standard medication to prevent the transmission of the human immunodeficiency virus from mother to fetus. The present study was designed to assess the acoustic startle response (ASR) in adult rats that had been perinatally exposed to AZT. Each litter was randomly assigned to a treatment group: nontreated, AZT 0, 50, 100 or 150 mg/kg. Once daily gastric intubation began prenatally between gestational day (G) 19 and 22 and then continued postnatally between postnatal day (PND) 2 and 20. Between PND75 and PND80, animals were tested for habituation to the acoustic stimuli and prepulse inhibition following a challenge of either saline or 1.0 mg/kg amphetamine (AMP) intraperitoneally. Amphetamine increased ASR and startle latencies throughout the session. The AZT100 dose increased ASR habituation. AZT treatment did not affect prepulse inhibition. Females treated with AZT150 continued to show high ASRs at the end of the startle session. AZT-treated animals showed a dose-dependent increase in peak latency, suggesting a possible abnormal conduction velocity. These effects are independent of handling and intubation effects. Therefore, perinatal AZT treatment results in long-term changes within the primary acoustic startle pathway.     

Effects of l-tetrahydropalmatine on locomotor sensitization to oxycodone in mice

Aim: Recent studies have shown that l-tetrahydropalmatine (l-THP), an active component of Corydolis yanhusuo, can inhibit the development of the conditional place preference induced by opioid receptor agonists, but the effects of l-THP on locomotor sensitivity induced by opioid receptor agonists have not been documented. In the present study, the effects of l-THP on locomotor sensitization to oxycodone, which is an opioid receptor agonist, were studied. Methods: Mice treated daily for 7d with 5mg/kg oxycodone and challenged with the same dose after 5 days of washout showed locomotor sensitization. In order to study the effects of l-THP on locomotor sensitization induced by oxycodone, l-THP was administered at doses of 6.25, 12.5, and 18.75mg/kg, 40min prior to treatment of oxycodone. Results: l-THP per se did not affect the locomotor activity at the doses of 6.25, 12.5, and 18.75mg/kg, but could antagonize the hyperactivity induced by oxycodone (5mg/kg). Co-administration of l-THP (18.75mg/kg), 40min prior to oxycodone, could inhibit the development of sensitization to oxycodone.In addition, l-THP (6.25, 12.5, and 18.75mg/kg, ig) dose-dependently prevented the expression of oxycodone sensitization. Conclusion: These results suggested that l-THP could attenuate the locomotor-stimulating effects of oxycodone and inhibit the development and expression of oxycodone behavioral sensitization.     

Infusions of bicuculline to the ventral tegmental area attenuates sexual, exploratory, and anti-anxiety behavior of proestrous rats

Actions of 5α-pregnan-3α-ol-20-one (3α,5α-THP), in the midbrain ventral tegmental area (VTA) modulate sexual receptivity of female rats. Actions of 3α,5α-THP at GABAergic substrates in the VTA are known to modulate consummatory aspects of sexual behavior among rodents, such as lordosis. However, the extent to which GABA_A receptors in the VTA are important for appetitive (exploratory, anti-anxiety, social) aspects of sexual receptivity is not well-understood. Proestrous rats were bilaterally-infused with saline or bicuculline (100 ng), a GABA_A receptor antagonist, to the VTA or missed control sites. Rats were assessed for exploratory/anti-anxiety (open field/elevated plus maze), social (social interaction), and sexual (paced-mating) behavior. Compared to saline or missed site controls, intra-VTA bicuculline significantly reduced the number of central entries in an open field, time spent on the open arms of an elevated plus maze, frequency and intensity of lordosis, anti-aggression towards a male, pacing of sexual contacts, and 3α,5α-THP concentrations in midbrain and hippocampus. Bicuculline-infused rats also displayed less affiliation with a novel conspecific, fewer sexual solicitations, and had lower 3α,5α-THP concentrations in diencephalon and cortex, albeit these were not significant differences. Thus, actions at GABA_A receptors in the midbrain VTA are essential for appetitive and consummatory aspects of sexual receptivity among rats.     

Developmental exposure to corticosterone: behavioral changes and differential effects on leukemia inhibitory factor (LIF) and corticotropin-releasing hormone (CRH) gene expression in the mouse

Rationale Cytokines are found in both the peripheral and central nervous system. There has been increasing interest in their potential role in some of the behavioral features of depressive disorders. Leukemia inhibitory factor (LIF), a proinflammatory cytokine, produces stimulation of adrenocorticotropic hormone (ACTH) secretion in response to emotional and inflammatory stress and recently has been linked to depressive-type behavior. Both the hypothalamic–pituitary–adrenal axis and the immune system, including cytokine-mediated responses, appear to be susceptible to long-term programming during fetal and neonatal development. Objective The present study was designed to characterize the effects of perinatal exposure to corticostereone on behavior, hypothalamic LIF and corticotropin-releasing hormone (CRH) mRNA expression, and basal plasma corticosterone levels in adult female mice. Methods Corticosterone was added to the drinking water beginning the last week of gestation and continued until weaning. Behavior in the open field and forced swim tests, baseline plasma corticosterone levels, and hypothalamic LIF and CRH gene expression were evaluated in the adult offspring. Results Mice exposed to perinatal corticosterone showed increased immobility in the forced swim test and increased locomotor activity in the open field test. Although there were no differences between treatment groups in terms of basal plasma levels of corticosterone or hypothalamic CRH mRNA, LIF mRNA expression was increased in the hypothalamus. Conclusions These results show that perinatal exposure to glucocorticoids can produce long-term behavioral changes and upregulation of central LIF mRNA expression.     

In utero and lactational exposure to PCB 118 and PCB 153 alter ovarian follicular dynamics and GnRH-induced luteinizing hormone secretion in female lambs

The effects of in utero and lactational exposure to two structurally different polychlorinated biphenyl (PCB) congeners on follicular dynamics and the pituitary-gonadal axis in female lambs were investigated. Pregnant ewes received corn oil, PCB 118, or PCB 153, and offspring was maintained until 60 days postpartum. Ovarian follicles were quantified using stereology. Plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured using radioimmunoassay before and after administration of a gonadotropin releasing hormone (GnRH) analog. PCB 118 exposure increased numbers of transitional, secondary, and the sum of secondary, early antral, and antral (Σsecondary-antral) follicles, PCB 153 exposure only increased the number of primary follicles. GnRH-induced LH levels were significantly elevated in the PCB 153 exposure group. We conclude that PCB 153 and PCB 118 alter follicular dynamics in lambs and modulate the responsiveness of the pituitary gland to GnRH.     

Effect of prolonged exposure to nicotine and stress on the pituitary-adrenocortical response; the possibility of cross-adaptation

Daily IP injections of nicotine (200 μg/kg body weight) resulted in an adaptation of the nicotine induced rise in plasma corticosterone. By 30 days the plasma corticosterone rise was not significantly different from that seen in control animals receiving an injection of saline. A similar adaptation to the plasma corticosterone response to the stress of signalled, irregular footshock was also observed. However, in the case of the exposure to stress, while the corticosterone response at day 40 was significantly less than the response seen on day 1, it was still significantly greater than the plasma corticosterone level from unstressed control animals. Cross-adaptation experiments were conducted in which animals were adapted to the steroidogenic action of nicotine and then subjected to a novel exposure to footshock stress, and vice versa. In both situations the animals responded to the novel stimulus, either stress or nicotine, with a significant rise in plasma corticosterone. It was postulated that nicotine and psychological stress act upon the hypothalamo-pituitary-adrenal axis via functionally separate pathways at the level of the corticotrophin releasing factor neuron. The separate pathways appear to differ in their ability to be inhibited by corticosterone feedback.     

Influence of repeated cocaine exposure on the endocrine and behavioral responses to stress in rats

Previous studies have determined that chronic cocaine exposure inhibits the serotonergic stimulation of hormone secretion. The present experiments were conducted to determine whether the endocrine responses to stress could be a useful approach to assess the influence of cocaine exposure on neuronal function. Male rats received twice daily injections of cocaine (1–15 mg/kg, IP) for 7 days. Animals were subsequently exposed to different stressors, i.e. conditioned emotional stress utilizing a low (0.5 mA) or high (1.5 mA) intensity footshock during training, or to immobilization stress. Immediately after the stress procedures, blood samples were collected for radioimmunoassay of plasma corticosterone, prolactin, and renin concentrations. Repeated cocaine exposure attenuated the stress-induced elevations of corticosterone and prolactin secretion, and attenuated some of the behavioral effects of the low intensity conditioned emotional stress. When exposed to the high intensity conditioned emotional stress, cocaine did not alter the endocrine or behavioral effects of stress. Finally, repeated cocaine exposure modified the immobilization stress-induced elevation of renin secretion; low doses of cocaine (1 or 5 mg/kg) attenuated, while higher doses (10 mg/kg) potentiated the renin response to immobilization stress. Thus, the influence of repeated cocaine exposure on the endocrine and behavioral responses to stress appears to depend upon the type and intensity of the stressor. Compared with previous studies which found altered neuroendocrine responses to serotonin releasers and agonists following cocaine exposure, the hormonal responses to stress are less consistently modified by cocaine.     

Chronic all-trans retinoic acid administration induced hyperactivity of HPA axis and behavioral changes in young rats

Although clinical reports suggest a possible relationship between excess retinoids and the development of depression, the effect of retinoids on mood-related behavior remains controversial. Hyperactivity of the hypothalamus–pituitary–adrenal (HPA) axis plays a key role in the development of affective disorders. The present study aimed to elucidate the effect of retinoid on the activity of HPA axis in rat and whether this goes together with behavioral changes. All-trans retinoic acid (ATRA) was administered to juvenile male rats by daily intraperitoneal injection for 6 weeks. ATRA treatment increased basal serum corticosterone concentration as well as the thickness of adrenal cortex in young rat. Furthermore, the mRNA expression of corticotropin release factor (CRF) and retinoic acid receptor-α (RAR-α) in the hypothalamus was both markedly increased in ATRA-treated rats compared with vehicle. Some behavioral alterations were also observed. ATRA-treated rats showed anxiety-like behavior in elevated-plus maze and decreased spontaneous exploratory activities in novel open field. However, in the sucrose preference test chronic ATRA treatment did not modify behavior in the juvenile animals. Chronic administration of ATRA did not impair physical motor ability in either the prehensile traction or the beam balance/walk test. In conclusion, long-term ATRA administration resulted in hyperactivated HPA axis which was accompanied by several behavioral changes in young rat.     

Effects of Electromagnetic Radiation Exposure on Stress-Related Behaviors and Stress Hormones in Male Wistar Rats

Studies have demonstrated that electromagnetic waves, as the one of the most important physical factors, may alter cognitive and non-cognitive behaviors, depending on the frequency and energy. Moreover, non-ionizing radiation of low energy waves e.g. very low frequency waves could alter this phenomenon via alterations in neurotransmitters and neurohormones. In this study, short, medium, and long-term exposure to the extremely low frequency electromagnetic field (ELF-EMF) (1 and 5 Hz radiation) on behavioral, hormonal, and metabolic changes in male Wistar rats (250 g) were studied. In addition, changes in plasma concentrations for two main stress hormones, noradrenaline and adrenocorticotropic hormone (ACTH) were evaluated. ELF-EMF exposure did not alter body weight, and food and water intake. Plasma glucose level was increased and decreased in the groups which exposed to the 5 and 1Hz wave, respectively. Plasma ACTH concentration increased in both using frequencies, whereas nor-adrenaline concentration showed overall reduction. At last, numbers of rearing, sniffing, locomotor activity was increased in group receiving 5 Hz wave over the time. In conclusions, these data showed that the effects of 1 and 5 Hz on the hormonal, metabolic and stress-like behaviors may be different. Moreover, the influence of waves on stress system is depending on time of exposure.     

Potentiation of glucocorticoid release does not modify the long-term effects of a single exposure to immobilization stress

Rationale Previous work has shown that a single exposure of rats to a severe stressor (immobilization, IMO) results, days to weeks later, in a reduced response (desensitization) of the hypothalamic–pituitary–adrenal (HPA) axis to a second exposure to the same stressor.Objectives In the present work, we studied the influence of both length of exposure to IMO and circulating levels of corticosterone on the first day on the degree of desensitization of two sets of physiological variables: HPA hormones and food intake.Methods Rats were given SC saline or ACTH administration and then exposed to IMO for 0, 1 or 20 min. Seven days later, all rats were exposed to 20 min IMO. HPA response was followed on both experimental days by repeated blood sampling and food intake was measured on a 24-h basis.Results Both ACTH administration and IMO activates the HPA axis and IMO reduced food intake for several days. A single previous experience with IMO enhanced the post-IMO return of HPA hormones to basal levels on day 8 and reduced the degree of anorexia. The protective effect of previous IMO on food intake was independent of, whereas that on HPA activation was positively related to, the length of exposure on day 1. Concomitant ACTH administration on day 1 did not modify the observed effects.Conclusions Long-term protective effects of a single exposure to IMO are observed even with a brief exposure, but they are not potentiated by increasing corticosterone levels during the first exposure.     

Enhancement of the ACTH response to human CRH by pretreatment with the antiglucocorticoid RU-486

Summary The response of ACTH to an i.v. bolus injection of 100 µg human CRH at 09.00 h was investigated in five healthy men with and without pretreatment with the antiglucocorticoid RU-486 100 mg given orally 7 h before the injection of CRH. In all five subjects the plasma cortisol level immediately before CRH administration at 09.00 h was significantly higher after pretreatment with the antiglucocorticoid (17.1 vs 11.1 µg/100 ml). Despite this higher baseline cortisol level, in all subjects the maximal CRH-induced ACTH increase was more pronounced after RU-486 loading (_max ACTH 39 vs 26 pg/ml). This observation proves that in man physiological concentrations of cortisol determine the response of the pituitary to CRH. Furthermore, the findings suggest reduced circulating glucocorticoid activity after administration of 100 mg RU-486, not completely compensated by an increase in plasma cortisol.     

Prenatal ethanol exposure enhances the susceptibility to metabolic syndrome in offspring rats by HPA axis-associated neuroendocrine metabolic programming

Objective

The present study was designed to demonstrate that prenatal ethanol exposure (PEE) could enhance the susceptibility of high-fat diet-induced metabolic syndrome (MS) in adult male offspring via a hypothalamic–pituitary–adrenal (HPA) axis-associated neuroendocrine metabolic programmed mechanism.

Methods

Pregnant Wistar rats were intragastricly administrated ethanol 4 g/kg·d from gestational day 11 until term delivery. All male offspring were fed with high-fat diet after weaning, exposed to an unpredictable chronic stress at postnatal week (PW) 17 and sacrificed at PW20.

Results

In PEE group, body weight presented a “catch-up growth” pattern, and the HPA axis exhibited a lower basal activity but an enhanced sensitivity to chronic stress, leading to increased levels of serum glucose, insulin, insulin resistant index, total cholesterol and low-density lipoprotein-cholesterol, and decreased levels of high-density lipoprotein-cholesterol. Furthermore, many lipid droplets and vacuolar degeneration were observed in the hypothalamus, pituitary gland and liver.

Conclusions

PEE induces enhanced susceptibility to MS in adult offspring fed with high-fat diet, and the underlying mechanism involves a HPA axis-associated neuroendocrine metabolic programming alteration.     

Mid- to late gestational morphine exposure does not alter the rewarding properties of morphine in adult male rats

Prenatal exposure to drugs of abuse often leads to physiological and neurobiological abnormalities including decreased brain and body weight, cognitive deficits and behavioral alterations. A handful of studies showed increased vulnerability to drug abuse in prenatally drug-exposed offspring. Our work also demonstrated that prenatal exposure to analgesic doses of morphine during gestation days 11-18 increases mu-opioid receptor density in the nucleus accumbens and central amygdala of adult male rats. Both the nucleus accumbens and central amygdala play important roles in modulating drug-induced reward via the mesolimbic dopaminergic system. Therefore, two types of behavioral paradigms were used to test the hypothesis that the same prenatal morphine exposure would enhance the rewarding effects of morphine, making drug-exposed offspring more vulnerable to abuse this drug in adulthood. All experiments were performed with adult male offspring of saline-injected, morphine-injected or non-injected (control) dams. (1) The unbiased conditioned place preference (CPP) paradigm was used to investigate whether prenatal morphine exposure sensitizes adult male rats to non-contingent morphine reward. These adult animals were conditioned with 0.1, 0.3, 1, 3 or 5 mg/kg morphine. All control, prenatally saline- and morphine-exposed male rats preferred the morphine-paired compartment relative to the saline-paired compartment. However, the magnitude of morphine CPP in adult male rats was not dependent on the conditioning dose of morphine or prenatal morphine exposure. (2) Intravenous morphine self-administration was used to assess the behavioral response to contingent morphine reward. Each rat self-administered one of four doses of morphine (0.3, 1, 2 or 3 mg/kg/infusion). Morphine self-administration was not altered in prenatally morphine-exposed adult male offspring. Control males self-administered significantly less morphine at the lowest dose of morphine than both prenatally saline- and morphine-exposed males. Although our data show that prenatal exposure to an analgesic dose of morphine during the time of opioid receptor appearance does not enhance morphine CPP or self-administration, they do not exclude the possibility that this prenatal morphine exposure enhances the rewarding properties of other drugs of abuse.     

A preliminary study of dexamethasone treatment on pituitary–adrenal responsivity in major depression

Major depression is characterized by overactivity of the hypothalamic–pituitary–adrenal (HPA) axis. Dexamethasone (DEX), the glucocorticoid agonist, has been shown to be effective in the treatment of depression. We chose to examine the impact of a short course of DEX treatment on depressive symptomatology, and on the pituitary‐adrenal response to CRH administration. In this preliminary study, five subjects with major depression were treated for 4 days with 3 mg DEX; a CRH test was performed before and after treatment. Four subjects showed a reduction in ACTH (p=0·01) and cortisol output (p<0·01) following DEX treatment. All subjects showed a drop in depression scores after treatment; the Hamilton Depression score fell by 11·4±1·7 (mean±SEM) from baseline (p=0·01) and the Beck Depression score by 9·2±2·5 (mean±SEM) from baseline (p=0·01); this represented a reduction by almost 50 per cent from baseline levels on both depression indices. We suggest that the impact of DEX treatment on depressive symptoms may reflect a restraining influence on an overactive HPA, with a normalization of pituitary–adrenal response to CRH drive. Larger studies are required to investigate this further and to ascertain whether the mood and neuroendocrine changes induced by dexamethasone are sustained. Copyright © 1999 John Wiley & Sons, Ltd.     

Effects of ketoconazole on the acquisition of intravenous cocaine self-administration under different feeding conditions in rats

RATIONALE: Ketoconazole, an inhibitor of corticosterone synthesis, has been reported to decrease the self-administration of low doses of cocaine and prevent stress-induced reinstatement of cocaine-reinforced behavior in rats. OBJECTIVES: The effects of ketoconazole were extended to the acquisition of i.v. cocaine self-administration during food restriction, a form of stress. Food restriction accelerates the acquisition of cocaine self-administration, and the purpose of this experiment was to determine whether ketoconazole would block the food-restriction effect. As control conditions, the effects of ketoconazole on the acquisition of cocaine self-administration in food-satiated rats and acquisition of food-reinforced responding were also evaluated. METHODS: Six groups of rats (groups 1-6) were trained to self-administer i.v. cocaine (0.2 mg/kg; groups 1-4) or food pellets (45 mg; groups 5 and 6) under a fixed-ratio 1 (FR 1) schedule. Food availability was restricted to 20 g per day in groups 1, 2, 5, and 6, while groups 3 and 4 were fed ad libitum. Daily sessions included a 6-h autoshaping component followed by a 6-h self-administration component. During autoshaping, 10 infusions or food pellets were delivered each h under a random interval 15-s schedule after extension and retraction of a lever. During self-administration, the lever remained extended and infusions or food pellets were available under an FR 1 schedule. The criterion for acquisition was a 5-day period during which a mean of 100 cocaine infusions or 150 food pellets was obtained during the self-administration component. Rats were given 30 days to reach this criterion. They were pretreated with ketoconazole (25 mg/kg, i.p.; groups 1, 3, and 5) or vehicle (i.p.; groups 2, 4, and 6) 30 min prior to the autoshaping and self-administration components. RESULTS: Pretreatment with ketoconazole decreased both the rate of acquisition of cocaine self-administration and the percentage of rats meeting the acquisition criterion but only under food-restricted conditions. Ketoconazole had no effect on the acquisition of food-reinforced responding. CONCLUSIONS: These results extended previous findings of the suppressant effects of ketoconazole on cocaine-reinforced responding in rats to the acquisition of cocaine self-administration using food restriction as a stressor.     

围生期磺胺间甲氧嘧啶暴露对海马mTOR信号通路调控机制的影响

目的 探讨围生期磺胺间甲氧嘧啶暴露对海马雷帕霉素靶蛋白(mTOR)调控机制的影响。方法 选用40只美国癌症研究所(ICR)雌鼠从受孕后第1天(GD1)至仔鼠出生后21d(PND 21)，每天分别对其灌服1次10、50和200mg/kg的磺胺间甲氧嘧啶(SMM)和生理盐水，并用气相色谱法测定母鼠粪便中短链脂肪酸(SCFAs)，蛋白免疫印迹法检测PND 22和PND 56时雌性子鼠海马中mTOR信号通路相关蛋白的表达。结果 与对照组相比，各SMM处理组母鼠粪便中总短链脂肪酸(SCFAs)和丁酸含量显著下降(P＜0.05)；处理组雌性子鼠海马中蛋白激酶B(Akt)和mTOR以及低、中剂量组4E结合蛋白(4EBP1)表达明显增高(P＜0.05)；PND 56时，处理组磷脂酰肌醇-3-羟激酶(PI3K)和mTOR以及中、高剂量组核糖体蛋白S6激酶1(S6K1)表达均显著降低(P＜0.05)，处理组4EBP1表达明显增高(P＜0.05)。结论 围生期母鼠暴露SMM致其肠道菌群紊乱，间接诱导其雌性子代海马mTOR信号通路异常。     

Exposure of the amygdala to elevated levels of corticosterone alters colonic motility in response to acute psychological stress

The amygdala is important for integrating the emotional, endocrine and autonomic responses to stress. Exposure of the amygdala to elevated levels of corticosterone (CORT) induces anxiety-like behavior and a hypersensitive colon in rodents; however, effects on colonic transit are unknown. Micropellets releasing CORT alone or combined with a selective glucocorticoid (GR) or mineralocorticoid (MR) receptor antagonist were implanted bilaterally at the dorsal boundary of the central amygdala in male rats. Inactive cholesterol implants served as controls. Seven days later, rats received water avoidance stress (WAS) for 1 h and the fecal pellet output was measured. Colorectal transit was also evaluated following the stressor by recording the time for expulsion of a glass bead placed into the colorectum. Plasma CORT levels were evaluated before WAS, after 60 min of WAS and 90 min post-WAS. Exposure of the amygdala to elevated CORT did not alter daily fecal pellet production or the number of fecal pellets released in response to WAS. However, following WAS, rats with CORT implants on the amygdala showed a delay in colorectal transit compared to cholesterol-implanted controls. Plasma CORT measurements showed that basal and WAS-induced increases in plasma CORT were similar in all groups but a prolonged increase in plasma CORT was observed 90 after cessation of WAS in rats with CORT implants. The post-WAS changes in colonic motility and plasma CORT were prevented by antagonism of GR or MR in the amygdala, suggesting their importance in driving stress-associated changes in colonic motility.     

Effects of prenatal cigarette smoke exposure on neurobehavioral outcomes in 10-year-old children of adolescent mothers

In this prospective study, adolescent mothers (mean age = 16; range = 12-18; 70% African-American) were interviewed about their tobacco use during pregnancy. When their children were ten, mothers reported on their child's behavior and the children completed a neuropsychological battery. We examined the association between prenatal cigarette smoke exposure (PCSE) and offspring neurobehavioral outcomes on data from the 10-year phase (n = 330). Multivariate regression analyses were conducted to test if PCSE predicted neurobehavioral outcomes, adjusting for demographic characteristics, maternal psychological characteristics, prenatal exposure to other substances, and exposure to environmental tobacco smoke. Independent effects of PCSE were found. Exposed offspring had more delinquent, aggressive, and externalizing behaviors (CBCL). They were more active (Routh, EAS, and SNAP) and impulsive (SNAP) and had more problems with peers (SNAP). On the Stroop test, deficits were observed on the more complex interference task that requires both selective attention and response inhibition. The significant effects of PCSE on neurobehavioral outcomes were found for exposure to as few as 10 cigarettes per day. Most effects were found from first trimester PCSE exposure. These results are consistent with results from an earlier assessment when the children were age 6, demonstrating that the effects of prenatal tobacco exposure can be identified early and are consistent through middle childhood.