Influence of perinatal malnutrition and early handling on the pituitary-adrenal response to noxious stimuli in adult rats

A series of experiments examined the influence of perinatal malnutrition and infantile stimulation (preweaning handling) on the pituitary-adrenal response to novelty, electric shock and ether in adult rats. Neither early experience variable altered the magnitude or time course of the plasma corticosterone response to the combined stress of ether exposure and cardiac puncture. Although perinatal malnutrition did not change the magnitude of the adrenocortical response 15 min following a 1-min exposure to a novel test chamber alone or with 0.25 or 1.0 mA of scrambled electric shock, early handled subjects of both nutrition groups displayed lower corticoid elevations compared to nonhandled rats. Additionally, all subjects showed a lower corticoid elevation to the novel chamber without shock compared to the chamber plus electric shock, with females being able to display a differential corticoid response to the two shock levels. Perinatal malnutrition did not alter the magnitude and time course of the ACTH response to a 1-min exposure to a novel chamber alone or with ether. Thus, perinatal malnutrition does not appear to alter either the basal levels of ACTH and corticosterone or the response of these hormones following the stressors examined. Early handling modulated the response to novelty and electric shock but not ether, suggesting that the latter response is mediated by brain regions not influenced by infantile stimulation. Finally, the results of these studies indicate that the magnitude of the pituitary-adrenal response reflects different intensity levels of electric shock in female rats.     

The effects of age and isolation period on two phases of behavioral response to foot shock in isolation-reared rats

Using rats as subjects, the effects of a period of isolation and the subjects' age during isolation on the response to foot shock were systematically examined in three experiments. Both the thresholds of shock that evoked a jumping response and that evoked a thrashing response were measured. The results suggest that the threshold for jumping response decreased when rats were isolated during the postweaning stage of development. On the other hand, the threshold for thrashing response decreased when the subjects were isolated for more than 39 days, independently of their age during isolation. Possible causes of the differential effects of these two factors are discussed in relation to the developmental process of these two behavioral indices.     

Anxiogenic effect of chronic exposure to extremely low frequency magnetic field in adult rats

Previous study has suggested some relations between extremely low frequency magnetic field (ELF MF) and the emotional state of human beings and animals. The aim of the present study was to investigate whether the anxiety level could be affected by repeated ELF MF exposure of different daily durations. Adult SD rats were submitted to no exposure, MF exposure 1h/day or 4h/day for 25 days. Anxiety-related behaviors were examined in the open field test (OFT), the elevated plus maze (EPM), and light/dark box on the 21th, 23th and 25th exposure day, respectively. Results demonstrated that MF exposure 4h/day increased the anxiety-like behaviors in rats in the open field test and the elevated plus maze test, without altering their locomotor activity, but had no effect in the light/dark box test. Moreover, MF exposure 1h/day had no effect in any test. These findings indicate that chronic ELF MF exposure has anxiogenic effect in rats, which is dependent on the daily exposure duration and it is more sensitive to void space than to strong light.     

Genetic influences on behavioral and neuroendocrine responses to predator-odor stress in rats

The exposure of animals to a variety of stressful events can induce behavioral and physiological responses, which can be modulated by anxiety levels. It is well recognized that genetic factors play a substantial role in both anxiety and stress reactivity. The present study examined the effect of exposure to 2,4,5-trimethylthiazoline (TMT), a component of fox feces, on nociception and corticosterone levels in Lewis (LEW) and Spontaneously Hypertensive (SHR) inbred rat strains (which display genetic differences in anxiety models such as the elevated plus-maze and open-field). The influence of two quantitative trait loci (QTL), named Ofil1 and Ofil2, which are known to affect emotionality in LEW versus SHR intercrosses on the responses to TMT was also investigated. LEW and SHR rats of both sexes displayed similar levels of behavioral and neuroendocrine responses after TMT exposure. As expected, TMT odor stress produced analgesia and enhanced corticosterone levels. Ofil1 on chromosome 4 affected stress-induced analgesia in males only. Ofil2 on chromosome 7 had no effect. The results suggest that behaviors measured in classical models of generalized anxiety and reactivity to stress produced by predator odors can be genetically dissociated. Finding a locus with an effect on the behavioral responses to stress represents the starting point in the search for genes responsible for stress-related traits.     

Short-term exposure to alcohol in rats affects brain levels of anandamide, other N-acylethanolamines and 2-arachidonoyl-glycerol

Chronic alcohol exposure leads to significant changes in the levels of endocannabinoids and their receptors in the brains of humans and laboratory animals, as well as in cultured neuronal cells. However, little is known about the effects of short-term periods of alcohol exposure. In the present study, we examined the changes in endocannabinoid levels (anandamide and 2-arachidonoylglycerol), as well as four additional N-acylethanolamines, in four brain regions of rats exposed to alcohol through the liquid diet for a period of 24h. The levels of N-acylethanolamines were diminished 24h after the onset of alcohol exposure. This was particularly evident for anandamide in the hypothalamus, amygdala and caudate-putamen, for N-palmitoylethanolamine in the caudate-putamen, for N-oleoylethanolamine in the hypothalamus, caudate-putamen and prefrontal cortex, and for N-stearoylethanolamine in the amygdala. The only exception was N-linoleoylethanolamine for which the levels increased in the amygdala after the exposure to alcohol. The levels of the other major endocannabinoid, 2-arachidonoylglycerol, were also reduced with marked effects in the prefrontal cortex. These results support the notion that short-term alcohol exposure reduces endocannabinoid levels in the brain accompanied by a reduction in several related N-acylethanolamines.     

Family history of hypertension,exercise training,and reactivity to stress in rats

In this study we sought to assess the role of exercise training on blood pressure (BP) reactivity to tailshock stress in rats with varying family histories of hypertension. Exercise training consisted of swimming 90 min per day in isothermic water for either 2, 6, or 10 months, beginning at 2 months of age. Control subjects were age-matched and did not exercise daily. Rats with either zero (Wistar-Kyoto), 1 (borderline hypertensive), or 2 (spontaneously hypertensive) hypertensive parents were studied. At the appropriate age, femoral artery catheters were implanted and rats were studied at rest and in response to a 20-min stress session. Exercise training reduced basal BP, especially in rats with a positive family history that were exercised for the longest duration. Reactivity to stress was actually significantly enhanced in trained rats. Thus, these data do not support the reactivity hypothesis, but suggest several reasons why the literature has been so inconsistent. The discussion emphasizes the importance of basal, rather than phasic, BP responses resulting from exercise training. Research for this article was supported by National Institutes of Health (NIH) Grant No. HL19680 to James E. Lawler and NIH Grant No. HL34878 to Ronald H. Cox     

Further analysis of behavioral and endocrine consequences of chronic exposure of male Wistar rats to subtoxic doses of endocrine disruptor chlorobenzenes

Many chemicals utilized by humans are present as environmental pollutants and may influence homeostasis from neurological, immunological, endocrinological and/or behavioral aspects. Such agents, acting alone or in ambient mixtures, may be biologically active even at extremely low doses, and it may be postulated that stable, bioaccumulative, reactive endorine disruptors may affect central and/or peripheral secretion of arginine-vasopressin (AVP) and oxytocin (OXT) and thereby related physiological and behavioral functions, potentially leading to disorders in exposed subjects. The primary aim of this study was to demonstrate effects of chronic exposure to a low dose of an orally administered chlorobenzene mixture on anxiety-related and aggressive behavior mediated largely by AVP and OXT. Chlorobenzenes were applied to model ambient mixtures of endocrine disruptors. Adult, male Wistar rats were exposed daily to 0.1 μg/kg of 1,2,4-trichlorobenzene and hexachlorobenzene via a stomach tube for 30, 60 or 90 days, after which anxiety-related and aggressive behavioral elements were examined in open-field, elevated plus maze and resident-intruder tests. The plasma levels of AVP, OXT and adrenocorticotrophic hormone at the endpoints were measured by radioimmunoassay or immunochemiluminescence assay. The levels of basal and serotonin- or norepinephrine-stimulated AVP and OXT secretion in pituicyte cultures prepared from the posterior lobe of the pituitaries were also measured. The hormone levels proved to be increased to extents depending on the duration of exposure to the chlorobenzenes. Several anxiety-related and aggressive behavioral elements were also enhanced following chlorobenzene exposure, while certain explorative and locomotive elements of the animals were decreased. As both physiological and behavioral elements were modulated by chronic, subtoxic doses of chlorobenzenes, it is concluded that doses of such environmental pollutants low enough to fall outside the range of legal regulation may pose potential risks of anxiogenic and/or aggressive consequences in exposed subjects, including humans.     

p27kip1和Skp2在大鼠坐骨神经夹伤后脊髓中的表达变化

目的:研究p27~(kip1)和Skp2在正常和坐骨神经夹伤后大鼠脊髓中的表达变化。方法:Westem印迹法,免疫组织化学,免疫荧光双标。结果:Western印迹结果显示坐骨神经夹伤后,脊髓中p27~(kip1)表达下降后又有所恢复,并且p27~(kip1)和Skp2在脊髓中的表达变化呈负相关。免疫组织化学及免疫荧光双标显示,p27~(kip1)和Skp2在正常和损伤后的脊髓神经元和胶质细胞中都有表达。坐骨神经夹伤后p27~(kip1)和Skp2在脊髓腹角阳性细胞数目变化呈负相关。结论:坐骨神经损伤后p27~(kip1)。和Skp2在脊髓腹角神经元及其周围的胶质细胞表达变化相关,对研究脊髓损伤和修复的分子机制有重要意义。     

Acute release of cytokines is proportional to tissue injury induced by surgical trauma and shock in rats

Cytokines are important mediators of the inflammatory reaction and microvascular injury after trauma and tissue ischemia. The plasma activity of a cytokine reflects the net effect of positive and negative signals. We examined the sequential serum activity of IL-1, IL-2, IL-6, and TNF in a severe model of splanchnic artery occlusion (SAO) shock induced in rats by total occlusion of the superior mesenteric and the celiac arteries for 40 min. A control group with negligible surgical intervention and two sham-shock groups, one with minor operation and another with major surgery employed in SAO rats, both without vascular occlusion, were also studied. No IL-1 activity was detected throughout the 190-min experimental protocol in any of the groups. Low activity of IL-2 was measured only in SAO rats (1 U/ml at the peak). We found graded increases in serum TNF and IL-6 activities which were proportional to the surgical trauma and were highest in SAO rats (IL-6 up to 30 U/ml,P<0.01 from both sham groups; TNF, 2500 pg/ml 30 min after reperfusion,P<0.01 from both sham groups). These data further support the role played by cytokines in the early mediation of surgical trauma and shock.This study was carried out in adherence with the NIH guidelines for the use of experimental animals.     

2,3,7,8-四氯苯二噁英宫内暴露对子鼠肾细胞及其亚细胞结构的毒性影响

目的 探讨妊娠早期母鼠接触2,3,7,8-四氯苯二噁英(TCDD)后对子代新生鼠肾的毒性影响.方法 妊娠13d的SD雌性大鼠随机分为对照组、玉米油组和染毒组(每组6只),观察3组大鼠出生3d雌性鼠的肾细胞及其亚细胞结构差异.结果 对照组子鼠和玉米油组子鼠的肾,不论是细胞结构还是亚细胞结构均未见病理改变.染毒组中,5 n...     

Hyper-responsiveness of adrenal sympathetic nerve activity in spontaneously hypertensive rats to ganglionic blockade, mental stress and neuronglucopenia

 Previous investigations indicate that the spontaneously hypertensive rat (SHR) has elevated sympathetic tone at rest. The present study aimed to determine whether SHR has exaggerated sympatho-adrenal activation in response to various sympathetic stimuli. The mean blood pressure (MBP), heart rate (HR) and preganglionic adrenal sympathetic nerve activity (SNA) were recorded from conscious, unrestrained SHR and from its normotensive control, the Wistar-Kyoto rat (WKY) (n=7, respectively).Ganglionic blockade (trimethaphan, 5 mg/kg) reduced MBP identically in both groups of rats. It did not change HR in SHR, but increased HR significantly in WKY (P<0.05). The adrenal SNA increased in both groups, but the magnitude of the increase was more than threefold greater in SHR (P<0.05). Mental stress caused by air-jet induced significantly greater tachycardia (threefold) and sympatho-adrenal activation (tenfold) in SHR than in WKY rats. In SHR the inhibition of glycolysis (2-deoxy-d-glucose, 500 mg/kg) also produced a profound activation of adrenal SNA (sevenfold) and the increased adrenal SNA was not paralleled by an increased HR. We conclude that a variety of sympathetic stimuli, including ganglionic blockade, mental stress and neuronglucopenia, cause exaggerated activation of preganglionic adrenal SNA in SHR compared with WKY, indicating that adrenal SNA in SHR is hyper-responsive. Received: 26 May 1998 / Received after revision: 30 July 1998 / Accepted: 11 August 1998     

Individual differences in the cortisol response to stress in young healthy men: testing the roles of perceived stress reactivity and threat appraisal using multiphase latent growth curve modeling

Individual differences in stress reactivity and cognitive appraisal processes are thought to explain part of the heterogeneity in stress responses. This study investigated how perceived typical stress reactivity and momentary cognitive appraisal affect salivary cortisol responses to a laboratory performance stressor with social evaluation in 66 male non-smokers. Multiphase latent growth curve models showed positive associations of perceived stress reactivity and primary appraisal with cortisol responses. An age-adjusted path analysis suggested that primary appraisal mediated the effect of perceived reactivity to social evaluation on cortisol responses, and that effects of primary appraisal were attenuated at high levels of perceived reactivity. Our results suggest that individuals who report that they typically show strong perceived emotional, cognitive and autonomic responses to social evaluative stress tend to perceive the prospect of having to perform in front of an audience as more threatening, and that this appraisal then leads to stronger cortisol responses.