Yoshishige Ida

Time-related differences in noradrenaline turnover in rat brain regions by stress

Male Wistar rats were stressed by immobilization from 15 to 180 min and the effect on noradrenaline (NA) and 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO4) contents in eight discrete brain regions were determined. NA levels significantly decreased and MHPG-SO4 levels increased in the hypothalamus, amygdala, thalamus, hippocampus, pons+ med.obl. and cerebral cortex. By contrast, the basal ganglia exhibited increases in NA levels and transient decreases in MHPG-SO4 levels. The midbrain failed to show significant alterations. The most rapid and marked increase in MHPG-SO4 level was found in the hypothalamus. When rats were exposed to stress after treatment with probenecid 400 mg/kg, the hypothalamus and amygdala showed greater accumulations of MHPG-SO4 in the early phase of stress, while the pons+ med.obl. and basal ganglia in the later phase. The other regions showed virtually the same accumulations. These results suggest that NA release is enhanced by immobilization in the six regions mentioned above and that response of NA neurons occurs rapidly in the hypothalamus and amygdala but is delayed in other regions.

Psychological stress enhances noradrenaline turnover in specific brain regions in rats

Concentrations of noradrenaline (NA) and 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO4) in the hypothalamus, amygdala, cerebral cortex and pons + medulla oblongata were examined in male Wistar rats exposed to foot-shock or to psychological stress for 1 hour. Animals in the psychological stress group were prevented from receiving foot shock, but were exposed to responses of shocked rats. Foot shocked rats exhibited a significant reduction in NA content and a significant elevation in MHPG-SO4 level in all brain regions when compared to control rats which were neither shocked nor exposed to shocked rats. Rats exposed to the psychological stress displayed a significant reduction of NA level in the amygdala, significant elevation of MHPG-SO4 content in the hypothalamus and amygdala, and a moderate elevation of plasma corticosterone level. These results suggest that psychological stress produces mild enhancement of NA release preferentially in the hypothalamus and amygdala; while foot shock stress elicits a more intense response of noradrenergic neurons in more extended brain regions.

Regional characteristics of stress-induced increases in brain noradrenaline release in rats

Male Wistar rats were exposed to immobilization stress for various periods (1 to 5 hr) with or without an IP injection of probenecid at 400 mg/kg. The regional characteristics of stress-induced increases in noradrenaline (NA) release in the rat brain related to the time-course of stress were demonstrated by measuring levels of the major metabolite of NA, 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO4). Increases in MHPG-SO4 levels occurred mainly within the first hr of stress in the hypothalamus, amygdala and thalamus, while the peak elevations of the metabolite levels were delayed in the hippocampus, cerebral cortex, pons + medulla oblongata and basal ganglia. According to the accumulation of MHPG-SO4 during each 1-hr period of stress, regional characteristics of NA release were classified into the following four types based upon regions where the most marked increase in MHPG-SO4 levels occurs mainly: (1) within the first hr of stress (the hypothalamus, amygdala and thalamus), (2) during the first and second hr (the hippocampus and cerebral cortex), (3) during the third hr (the basal ganglia) and (4) to the same extent from the first to the fourth hr of stress (the pons + medulla oblongata). These results suggest that noradrenergic neurons in different brain regions respond differentially to stress and reflect their own characteristic patterns depending upon nature and time-course of the stressor.

Differential effects of morphine on noradrenaline release in brain regions of stressed and non-stressed rats

Effects of morphine on noradrenaline (NA) turnover in the 8 brain regions were investigated in non-stressed and stressed rats. Morphine at 3 mg/kg and 6 mg/kg caused dose-dependent increases in levels of 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO4), the major metabolite of brain NA, in the hypothalamus, amygdala, thalamus, hippocampus and midbrain and decreases in NA levels in the first 4 of these regions. In contrast to these enhancing effects of morphine on NA release in non-stressed rats, pretreatment with morphine at 6 mg/kg significantly attenuated immobilization-stress-induced increases in MHPG-SO4 levels in the above regions. The morphine effects in both states, non-stressed and stressed, were reversed by naloxone at 0.5 mg/kg and 5 mg/kg in the hypothalamus, amygdala and thalamus. These neurochemical changes are apparently related to the distress-evoked hyperemotionality. Behavioral changes observed during the restraint stress such as struggling, vocalization and defecation were attenuated by morphine at 6 mg/kg and enhanced by naloxone at 5 mg/kg, and this action of morphine was also reversed by naloxone at 5 mg/kg. These results suggest that morphine acts to attenuate stress-induced increases in NA release in the hypothalamus, amygdala and thalamus via opiate receptors, although the drug facilitates NA release in these regions in non-stressed rats. Together with previous findings that naloxone enhances stress-induced increases in NA release selectively in these regions, it is further suggested that endogenous opioids released during stress might act to inhibit NA release in these specific brain areas and that these decreased noradrenergic activities might be closely related to the relief of the distress-evoked hyperemotionality in animals.

Attenuating effect of diazepam on stress-induced increases in noradrenaline turnover in specific brain regions of rats: antagonism by Ro 15-1788

One-hour immobilization stress increased levels of the major metabolite of brain noradrenaline (NA), 3-methoxy-4-hydroxyphenyl-ethyleneglycol sulfate (MHPG-SO4), in nine brain regions of rats. Diazepam at 5 mg/kg attenuated the stress-induced increases in MHPG-SO4 levels in the hypothalamus, amygdala, hippocampus, cerebral cortex and locus coeruleus (LC) region, but not in the thalamus, pons plus medulla oblongata excluding the LC region and basal ganglia. The attenuating effects of the drug on stress-induced increases in metabolite levels in the above regions were completely antagonized by pretreatment with Ro 15-1788 at 5 or 10 mg/kg, a potent and specific benzodiazepine (BDZ) receptor antagonist. When given alone, Ro 15-1788 did not affect the increases in MHPG-SO4 levels. Behavioral changes observed during immobilization stress such as vocalization and defecation, were also attenuated by diazepam at 5 mg/kg and this action of diazepam was antagonized by Ro 15-1788 at 10 mg/kg, which by itself had no effects on these behavioral measurements. These findings suggest: (1) that diazepam acts via BDZ receptors to attenuate stress-induced increases in NA turnover selectively in the hypothalamus, amygdala, hippocampus, cerebral cortex and LC region and (2) that this decreased noradrenergic activity might be closely related to relief of distress-evoked hyperemotionality, i.e., fear and/or anxiety in animals.

Naloxene enhances stress-induced increases in noradrenaline turnover in specific brain regions in rats

Male Wistar rats were injected subcutaneously with either saline or naloxone, 1 mg/kg or 5 mg/kg, 10 min before exposure to 1-hour immobilization-stress. Control animals were sacrificed 70 min after respective injections. Levels of noradrenaline (NA) and its major metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-S04) in seven discrete brain regions and plasma corticosterone levels were fluorometrically determined. Immobilization stress caused significant elevations of plasma corticosterone which were not affected by pretreatment with naloxone. In the hypothalamus, amygdala and thalamus, immobilization-stress caused significant elevations of MHPG-S04 levels, and naloxone at 5 mg/kg significantly enhanced these stress-induced elevations virtually without affecting the basal level of the metabolite. In contrast, in the hippocampus, cerebral cortex and pons plus medulla oblongata, MHPG-S04 levels were elevated by stress, but were not affected by naloxone pretreatment. The effect of naloxone on stress-induced reductions of NA levels was unclear, since naloxone by itself (5 mg/kg) significantly decreased the amine levels in 5 of 7 brain regions examined. These results indirectly suggest that endogenous opioid peptides in the hypothalamus, amygdala and thalamus are partly involved in the stress process and attenuate increases in NA turnover induced by stress.

Effects of acute and repeated alcohol ingestion on hypothalamic-pituitary-gonadal and hypothalamic-pituitary-adrenal functioning in normal males

We investigated the effects of acute and repeated alcohol ingestion on plasma levels of hormones associated with the functioning of the hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-adrenal (HPA) systems in normal males. In the first experiment, 7 normal male subjects were given ethanol (1.3 g/kg) in the form of a 43% alcohol solution of whiskey and water over a 30-min period (from 19:00 h to 19:30 h); blood samples were collected 30 min and immediately before the beginning of alcohol ingestion and then at intervals of 30 min for 180 min. Blood ethanol levels rose sharply and reached their maximum at 60 min, remaining above 1.0 mg/ml until 180 min. Prolactin levels increased, reaching a peak at 60 min, gradually returning to the initial value at 180 min. Decreased testosterone levels were observed only at 30 min. Luteinizing hormone (LH), adrenocorticotrophic hormone (ACTH) and cortisol levels did not show any increases. In the second experiment, 9 normal males were given the same dose of alcohol, but this was given on 7 consecutive evenings and the hormonal changes were examined on the 1st and 7th days, only at 30 and 60 min after alcohol ingestion began (during the period that blood ethanol levels were ascending to their peak). The results on the 1st day reconfirmed the findings in the first experiment and on the 7th day, the last alcohol ingestion produced increases in prolactin levels and decreases in testosterone levels at 30 and 60 min, but did not change other hormone levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Expression of aggression attenuates stress-induced increases in rat brain noradrenaline turnover

This experiment determined whether or not an aggressive biting response could attenuate stress-induced increases in brain noradrenaline (NA) turnover, by measuring contents of NA and its major metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO4), in discrete brain regions of male Wistar rats. Rats were exposed to a 10 min supine restraint stress with or without being allowed to bite a wooden stick. In each group, the animals were sacrificed by decapitation either 0 min or 50 min after release from stress. NA and MHPG-SO4 levels were unaffected in both biting and non-biting groups immediately after stress, as compared to controls. Fifty min after release from stress, increases in plasma corticosterone levels induced by stress recovered in the biting group but remained high in the non-biting group. MHPG-SO4 levels significantly increased in the hypothalamus, amygdala, thalamus, midbrain, basal ganglia, hippocampus and cerebral cortex in both stressed groups, however the increases in the non-biting group were significantly higher than those in the biting group in the first 5 of these regions. These findings clearly show that giving rats an opportunity to express aggression during stress exposure results in a significant attenuation of stress-induced increases in NA turnover in specific brain regions, such as the hypothalamus and limbic areas. The present experiment provides a possible neurochemical basis for clinical studies showing that suppression of anger in a stressful, frustrating situation leads to pathological consequences in humans.

Effects of preshock experience on enhancement of rat brain noradrenaline turnover induced by psychological stress

The present study examined alterations of brain noradrenaline (NA) turnover as a function of preshock and psychological stress treatments, by measuring contents of NA metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO4), in discrete brain regions of male Wistar rats. Psychological stress induced by exposing to the sight, sound and odor of other rats being shocked produced higher levels of MHPG-SO4 in the hypothalamus, amygdala and locus coeruleus (LC) region, as well as higher levels of plasma corticosterone. Preshock experienced rats also showed marked increases of MHPG-SO4 levels in the same regions described above and elevated plasma corticosterone levels when placed but not shocked in the same environment in which the rats had previously received shocks. The effects of psychological stress on brain NA turnover were affected by the animals shock history preferentially in the hypothalamus and amygdala. These results suggest that: a purely psychological stressor caused acutely enhanced NA turnover in specific brain regions; regional NA activity appeared to be reinstated simply by reexposure to the environment previously associated with shock; preshock experience further intensified the enhancement of amygdaloid NA turnover evoked by psychological stress. An additional experiment, studying the aftereffects of preshock experience, clearly showed that these findings result from sensitization or conditioning to the environment previously paired with shock, and not merely from the aftereffects of the shock per se.

Recovery of stress-induced increases in noradrenaline turnover is delayed in specific brain regions of old rats

Male Wistar rats at 2 and 12 months of age were sacrificed before, immediately following, and at 6 and 24 hours after a 3-hour immobilization stress period. Levels of noradrenaline (NA) and its major metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO4), in eight brain regions and plasma corticosterone levels were fluorometrically determined. Immobilization stress caused significant increases of MHPG-SO4 levels in all brain regions examined and significant elevations in plasma corticosterone levels in both 2 and 12 month old rats. In 2 month old rats, the MHPG-SO4 levels in all brain regions returned to control levels within 6 hours after release from the stress. However, in 12 month old rats, the metabolite levels in the hypothalamus, amygdala, pons plus medulla oblongata (pons+med. obl .) and midbrain still remained at significantly increased levels at 6 and 24 hours after the stress. Moreover, in the amygdala of older rats, stress-induced decreases in NA levels persisted even 6 hours after stress. Plasma corticosterone levels also showed significant elevations at 6 and 24 hours after the stress only in 12 month old rats. These results suggest that brain NA metabolism during recovery periods from an acute exposure to a stressful situation is altered by the aging process in such a manner that NA neurons in the hypothalamus, amygdala, pons+med. obl . and midbrain in older rats remain activated by stressful stimuli for prolonged periods of time following release from stress.