Adrenal gland responses to lipopolysaccharide after stress and ethanol administration in male rats

All forms of stress, including restraint stress (RS) and lipopolysaccharide (LPS) administration, activate the hypothalamic-pituitary-adrenal (HPA) axis. LPS binds to a recognition protein (CD14) and toll-like receptor 2/4 in different cells and tissues, including the adrenal gland, to induce the production of cytokines and cause upregulation of cyclooxygenase and nitric oxide synthase (NOS) enzymes. Acute ethanol exposure activates the HPA axis, but in some conditions prolonged administration can dampen this activation as well as decrease the inflammatory responses to LPS. Therefore, this study was designed to evaluate the adrenal response to a challenge dose of LPS (50 μg/kg) injected i.p., after submitting male rats to RS, twice a day (2 h each time) for 5 days and/or ethanol administration (3 g/kg) by gavage also for 5 days, twice daily. At the end of the experiment, plasma corticosterone concentrations and adrenal gland content of prostaglandin E (PGE) and NOS activity were measured as stress mediators. The results showed that repetitive ethanol administration attenuated the adrenal stress response to LPS challenge alone and after RS, by preventing the increase in plasma corticosterone concentrations and by decreasing the PGE content and NOS activity in the adrenal gland. Therefore, we conclude that moderate alcohol consumption could attenuate the effects of psychophysical stress and impair an inflammatory response.     

Altered stress responses in children exposed to early adversity: a systematic review of salivary cortisol studies

Pathological stress responses are implicated in numerous disorders. Hypothalamic-pituitary-adrenal axis function is influenced by gene-environment interaction, with early-life environmental adversity having long-lasting effects. We examine the evidence that, in humans, these effects are apparent from infancy. We systematically reviewed published findings on cortisol response to a stressor, in 0-5-year-olds already exposed to adversity. Adversity was defined as a negative environmental influence present post-conception. We searched Ovid MEDLINE (1950-May 2010), EMBASE (1980-May 2010) and PsychINFO (1806-May 2010). We included peer-reviewed, English language studies that analysed salivary cortisol before and after a standardised stressor. We identified 30 studies, of which 27 reported a significant effect of adversity on the cortisol response to stress. Six of these demonstrated an effect of prenatal substance exposure. Thirteen studies found that psychosocial adversity increased cortisol reactivity. Three studies reported that cortisol reactivity could be normalised by intervention programmes. The studies were heterogeneous, both in nature of adversity studied and in stressor used, precluding meta-analysis and assessment of publication bias. Our review presents evidence that adversity disrupts the stress response from an early age. Longitudinal studies are required to determine whether effects persist, alter with time, or are reversible with intervention.     

Reactivity and regulation in children prenatally exposed to cocaine

Children prenatally exposed to cocaine may be at elevated risk for adjustment problems in early development because of greater reactivity and reduced regulation during challenging tasks. Few studies have examined whether cocaine-exposed children show such difficulties during the preschool years, a period marked by increased social and cognitive demands and by rapid changes in reactivity and regulation. The authors addressed this question by examining frustration reactivity and regulation of behavior during a problem-solving task in cocaine-exposed and -unexposed preschoolers. Participants were 174 4.5-year-olds (M age = 4.55 years, SD = 0.09). Frustration reactivity was measured as latency to show frustration and number of disruptive behaviors, whereas regulation was measured as latency to approach and attempt the problem-solving task and number of problem-solving behaviors. Results indicated that cocaine-exposed children took longer to attempt the problem-solving task but that cocaine-exposed boys showed the most difficulties: They were quicker to express frustration and were more disruptive. Effect sizes were relatively small, suggesting both resilience and vulnerabilities.     

Memory and brain volume in adults prenatally exposed to alcohol

The impact of prenatal alcohol exposure on memory and brain development was investigated in 92 African-American, young adults who were first identified in the prenatal period. Three groups (Control, n=26; Alcohol-related Neurodevelopmental Disorder, n=36; and Dysmorphic, n=30) were imaged using structural MRI with brain volume calculated for multiple regions of interest. Memory was measured using the Verbal Selective Reminding Memory Test and its nonverbal counterpart, the Nonverbal Selective Reminding Memory Test, which each yielding measures of learning and recall. For both Verbal and Nonverbal Recall and Slope, linear trends were observed demonstrating a spectrum of deficits associated with prenatal alcohol exposure. Dysmorphic individuals performed significantly poorer than unexposed controls on 5 of 6 memory outcomes. Alcohol-exposed individuals demonstrated significantly lower total brain volume than controls, as well as lower volume in a number of specific regions including hippocampus. Mediation analyses indicated that memory performance associated with effects of prenatal alcohol exposure was mediated from dysmorphic severity through hippocampal volume, particularly right hippocampus. These results indicate that the association between the physical effects of prenatal alcohol exposure and deficits in memory are mediated by volumetric reduction in specific brain regions.     

Ethanol-induced grooming in mice selectively bred for differential sensitivity to ethanol

In rats, excessive grooming follows the application of several forms of stress. The injection of alcohol may be considered as a stressor, since it increases plasma corticosterone levels. The present study examines the effects of ethanol injections on grooming in two lines of mice selected for differences in their hypnotic response to ethanol, i.e., the long sleep (LS) and short sleep (SS) lines developed at the Institute for Behavior Genetics at the University of Colorado at Boulder. Various subhypnotic doses of ethanol produced excessive grooming in the SS line, but this did not occur in the LS line. The SS mice also displayed more "novelty-induced" grooming compared to the LS mice after repeated exposure to the testing situation. The increase in excessive grooming in both the ethanol-induced and the novelty-induced excessive grooming situations was most apparent in the second half of the observation period.     

Executive function in preschool children prenatally exposed to methadone or buprenorphine

Although an increasing number of children are born with prenatal methadone or buprenorphine exposure, little is still known about the potential long-term effects of these opioids. The aim of this study was to investigate executive function (EF) in children of women in opioid maintenance therapy (OMT). A total of 66 children (aged 48–57 months) participated in the study, 35 of which had histories of prenatal methadone or buprenorphine exposure. EF was measured using a battery of neuropsychological tests and the Behavior Rating Inventory of Executive Function—Preschool Version (BRIEF-P). Results showed that children of women in OMT perform lower on tasks of short-term memory and inhibition compared to nonexposed children, which was mainly associated with lower maternal education and employment rate. The OMT group scored significantly lower on all EF tasks compared to the nonexposed group, although scores fell within the average range on all measures. The development of these children should be monitored to assess for the possible problem behaviors and to promote optimal outcomes.     

Suggested behavioral interventions in the classroom to assist students prenatally exposed to drugs

The population of children exposed prenatally to alcohol, cocaine, methamphetamine, and other legal or illegal substances has been rapidly growing in America. The known characteristics of this group include deficits in rule-governed behavior, impulsivity, attention to task, language, sleep attachment, learning, social competence, coordination, hypersensitivity to environmental stimuli, and conduct problems. The purpose of this paper was to describe the characteristics of this population and match known, empirically demonstrated, data-based strategies, such as teacher attention and praise, token reinforcement programs, daily report cards, contingency contracting, self-instructional training, self-management, peer tutoring, Direct Instruction, and combining behavior therapy with stimulant medication therapy, to specific academic and social deficits in children with parental histories of substance abuse. © 1998 John Wiley & Sons, Ltd.     

Children prenatally exposed to maternal anxiety devote more attentional resources to neutral pictures

Maternal anxiety during pregnancy can negatively affect fetal neurodevelopment, predisposing the offspring to a higher risk of behavioral and emotional problems later in life. The current study investigates the association between maternal anxiety during pregnancy and child affective picture processing using event‐related brain potentials (ERPs). Mothers reported anxiety during the second trimester using the anxiety subscale of the Symptom Checklist (SCL‐90). At age 4 years, child affective picture processing (N = 86) was measured by recording ERPs during viewing of neutral, pleasant, and unpleasant pictures selected from the International Affective Pictures System. The late positive potential (LPP)—an ERP component reflecting individual differences in affective processing—was used as child outcome. The expected positive association between maternal anxiety and LPP amplitude for unpleasant pictures was not found. Nevertheless, we found a positive association between maternal anxiety during pregnancy and LPP amplitudes for neutral pictures in the middle and late time window at anterior locations (all p < .05). These associations remained significant after adjusting for maternal postnatal anxiety and gestational age at birth and after FDR correction for multiple comparisons. Our study provides neurophysiological evidence that children prenatally exposed to higher maternal anxiety devote more attentional resources to neutral pictures, but not to unpleasant pictures. Possibly, these children show enhanced vigilance for threat when viewing neutral pictures. Although useful in dangerous environments, this enhanced vigilance may predispose children prenatally exposed to higher maternal anxiety to developing behavioral and/or emotional problems later in life. A video abstract of this article can be viewed at: https://www.youtube.com/watch?v=kEzYi6IS2HA     

Influence of rearing conditions on voluntary ethanol intake and response to stress in rats

The effects of exposure to four environmental rearing conditions on subsequent voluntary ethanol intake and response to immobilization stress were examined. Male weanling rats were reared in an enriched environment, with a female partner, with a male partner, or individually, for 90 days. At 111 days of age, voluntary consumption of ethanol in increasing concentrations (3 to 9%, v/v) was assessed. Following the ethanol-exposure period, rats were randomly divided into stressed and nonstressed groups and exposed to 3 h of immobilization. Results indicated that the enriched animals consumed greater amounts of ethanol as compared to all other groups, suggesting that the enriched environment and not handling, housing conditions, or the presence of another male or female is responsible for the observed increase in ethanol drinking behavior. Ulcer data indicated that among environmentally enriched rats, ethanol attenuated stress ulcer development relative to their non-ethanol-exposed but stressed controls. In nonstressed enriched rats, ethanol alone exacerbated stomach damage. We suggest that environmental rearing conditions markedly influence the complex interaction between ethanol intake and the response to stress.     

Eyeblink classical conditioning and interpositus nucleus activity are disrupted in adult rats exposed to ethanol as neonates

Neonatal exposure to ethanol in rats, during the period of brain development comparable to that of the human third trimester, produces significant, dose-dependent cell loss in the cerebellum and deficits in coordinated motor performance. These rats are also impaired in eyeblink conditioning as weanlings and as adults. The current study examined single-unit neural activity in the interpositus nucleus of the cerebellum in adults following neonatal binge ethanol exposure. Group Ethanol received alcohol doses of 5.25 g/kg/day on postnatal days 4–9. Group Sham Intubated underwent acute intragastric intubation on postnatal days 4–9 but did not receive any infusions. Group Unintubated Control (from separate litters) did not receive any intubations. When rats were 3–7 mo old, pairs of extracellular microelectrodes were implanted in the region of the interpositus nucleus. Beginning 1 wk later, the rats were given either 100 paired or 190 unpaired trials per day for 10 d followed by 4 d of 100 conditioned stimulus (CS)-alone trials per day. As in our previous study, conditioned response acquisition in Group Ethanol rats was impaired. In addition, by session 5 of paired acquisition, Group Sham Intubated and Group Unintubated Control showed significant increases in interpositus nucleus activity, relative to baseline, in the CS–unconditioned stimulus interval. In contrast, Group Ethanol failed to show significant changes in interpositus nucleus activity until later in training. These results indicate that the disruption in eyeblink conditioning after early exposure to ethanol is reflected in alterations in interpositus nucleus activity.     

Role of the sympathetic nervous system in cerebrovascular responses to air-jet stress in rats

This study examined the role of sympathetic nerves in the control of cerebral hemodynamics during air-jet stress. In adult male Sprague-Dawley rats, blood flow velocity (pulsed Doppler) was measured in both internal carotid arteries 1 week after excision of one superior cervical ganglion. Blood pressure (BP) and carotid blood flows (CBFs) were simultaneously recorded during exposure to air-jet stress. In 5 out of 13 rats, stress was applied after β(2)-adrenoceptor blockade with ICI 118551 (0.4 mg/kg, then 0.2 mg/kg/h, i.v). Stress evoked an immediate rise in BP, CBFs, and vascular conductances. Vasodilatation was much larger on the denervated side than on the intact side (mean ± SEM: 78 ± 7 versus 19 ± 4%; P < 0.02) and lasted about 10 s. Thereafter, blood flows returned to or near normal and showed parallel variations while BP remained elevated. There was, therefore, a net vasoconstriction on both sides. In ICI 118551-treated rats, the initial vasodilatation was not significantly reduced on the denervated side (64 ± 4%), but the subsequent vasoconstriction was enhanced (P < 0.05) on both sides. In conclusion, air-jet stress evokes an immediate, short-lasting vasodilatation through a mechanism unrelated to β(2)-adrenoceptor stimulation. Sympathetic nerves powerfully limit this phenomenon, and thus contribute to protect the cerebral circulation from stress-induced BP surges.     

Effect of atropine or atenolol on cardiovascular responses to novelty stress in freely-moving rats

Cardiac hemodynamic mechanisms involved in cardiovascular responses to stress were studied in conscious, freely-moving female spontaneously hypertensive rats exposed for 15 min to an open-field. When pretreated with saline, the rats displayed a rapid rise in blood pressure, heart rate, aortic dP/dt and locomotor activity. In rats pretreated with 0.5 mg/kg of methylatropine, the tachycardia was slightly, but significantly reduced. In rats pretreated with 1 mg/kg of atenolol, the tachycardis and rise in dP/dt were markedly reduced. These data suggest that the cardiac responses to stress include predominantly cardiac sympathetic activation and a minor component of vagal withdrawal.     

Amygdala and periaqueductal gray lesions only partially attenuate unconditional defensive responses in rats exposed to a cat

Defensive responses to a cat were observed in rats given excitotoxic lesions of the central nucleus of the amygdala (ACe), dorsolateral periaqueductal gray (dlPAG), ventral periaqueductal gray (vPAG), or sham lesions. Rats were placed adjacent to a compartment containing a cat. Sham-lesioned rats avoided the area nearest the cat and preferred the area furthest away from the cat. They also exhibited numerous defensive responses including, climbing, escape from the apparatus, and freezing. Rats with lesions of the ACe reacted like the sham lesioned rats by preferring the area of the apparatus furthest from the cat, however they climbed and escaped significantly less than sham lesioned rats. Avoidance of the area adjacent to the cat was attenuated in rats with lesions of the vPAG. Climbing along the walls of the apparatus was also attenuated in rats with lesions of the vPAG. Escapes from the apparatus were not significantly reduced by lesions of the vPAG and dlPAG. Thus, ACe lesions attenuated climbing and eliminated escapes, but did not impair locomotion of the rat away from the cat.     

Conceptualizations of responses to stress

The article presents the concepts and methodologies used in a series of studies on responses to stress in different areas of life and in different age and social groups. The studies described include findings of the Bonn Longitudinal Study of Aging and several studies on reactions to stress, e.g. coping with chronic disease and other distressing life situations. The discussion of the empirical findings presented focuses on the concept of ‘response hierarchy’ and its possibilities for examining consistency in reactions to stress across time and different situations. The data presented emphasize the need for a process-centred view on stress and responding to stress in the context of a cognitive theory of personality comprehending the individual and her/his world as an undivisible dynamic unit.     

Cardiovascular responses to open-field stress in rats: sex differences and effects of gonadal hormones

We studied sex differences in cardiovascular responses to stress using a new radio-telemetry model in which freely-moving Spontaneously Hypertensive rats (SHR) are exposed to open-field novelty stress. This model allowed simultaneous assessment of cardiovascular and behavioural responses to psychological stress. Female SHR in the diestrous stage of their estrous cycle had markedly greater pressor and tachycardic responses to open-field exposure when compared to either female rats not in diestrous or male SHR. Treatment of ovariectomized SHR with estrogen alone had no significant effect on cardiovascular reactivity, while a combined treatment of estrogen and progesterone slightly, but significantly attenuated their pressor response to open-field stress. In addition, treatment of castrated male rats with testosterone significantly enhanced their pressor responses to stress when compared to values obtained before treatment. None of the hormone treatments had any significant effect on heart rate responses to stress. Neither at different stages of the estrous cycle nor after hormone treatments were there any marked changes in behavioural responses in the open-field, making it unlikely that the differences in cardiovascular stress responses were caused by changes in behavioural activity. These data demonstrate differences in cardiovascular stress responses that seem to be dependent on the stage of the estrous cycle. They suggest that particularly androgens, such as testosterone, may enhance pressor responses to stress. On the other hand, a combination of estrogen and progesterone, rather than estrogen alone, may have a small attenuating effect on cardiovascular reactivity.     

Galectin-3 decreases in mice exposed to immobilization stress

Using M3/38 monoclonal antibody we have analyzed effects of immobilization stress on the expression of galectin-3 in liver, spleen and peritoneal macrophages from adult RFM and C3H mice, as well as from aged C3H mice (total of 22 animals). In all analyzed tissues, immobilization stress caused a significant decrease in the expression of galectin-3, ranging from 14% to 47%. The decrease of galectin-3 was observed in both strains of mice, as well as in old animals. Moreover, the same range of decrease (approximately 50%) was observed when cells grown in vitro were exposed to subculturing, or heat-shock. Although the biological significance of this effect is not known, it is very interesting that a single episode of immobilization stress was sufficient to cause a significant decrease in galectin-3, implicating that this beta-galactoside-binding lectin might be involved in the physiological response to psychological stress.     

Increased novelty-induced grooming in aged rats: a preliminary observation

Age-related changes in grooming activity in female Fischer-344 rats were observed in a home cage and in a novel testing chamber for 50 min. Compared to the home cage condition with brief handling treatment, excessive grooming was found in the novel situation. The amount of novelty-induced grooming of aged rats (26-28 months) was about two times that of young animals (6-8 months). This increase in novelty-induced grooming of aged animals was attributable to an increase in the number of grooming bouts, prolongation of each grooming bout, and a slight increase in the duration of licking elements. However, there were no age differences in the percentage of face washing and the duration of face-washing elements. These results are discussed in terms of behavioral aging and age-related changes in peptidergic pathways in the brain.     

Affect expression in prenatally psychotropic exposed and nonexposed mother–infant dyads

This prospective study examined infant, maternal, and dyadic affective profiles at three months postpartum in infant–mother dyads that were exposed to psychotropic medications in utero compared with nonexposed control dyads. Control dyads of nondepressed mothers and their infants showed many similarities in affect expression with mother–infant dyads who were exposed to selective serotonin reuptake inhibitors (SSRIs) alone for treatment of maternal depression. In contrast, mothers who received SSRIs and Rivotril (Benzodiazepine derivative) for treatment of depression and anxiety expressed both positive and negative affect towards their infants. Clinical implications regarding use of psychotropic medications such as SSRIs alone or in combination with other drugs for treatment of maternal anxiety and depression during pregnancy are discussed. Clinicians should be aware of the possible differential response in maternal–infant interaction in a mixed diagnosis group (i.e., depression and anxiety) regarding infant temperament, possibly suggesting latent behavioral teratogenicity with psychotropics. ©2002 Michigan Association for Infant Mental Health.