Stress-induced Increases In Noradrenaline Release Research Articles

Expression of Aggression Attenuates Both Stress-Induced Gastric Ulcer Formation and Increases in Noradrenaline Release in the Rat Amygdala Assessed by Intracerebral Microdialysis

The effects of an aggressive biting response on stress-induced noradrenaline (NA) release in the rat amygdala and gastric ulcer formation were studied with an intracerebral microdialysis technique. Rats were exposed to a 60-min period of cold restraint stress with or without being allowed to bite a wooden stick. They were sacrificed 100 min after release from stress to investigate gastric ulcer formation. Cold-restraint stress increased NA release to 304 ± 22.3 and 206 ± 23.8% of basal levels (mean ± SEM) in the nonbiting and biting groups, respectively. The stress-induced increases in NA release in the nonbiting group were significantly higher than those in the biting group. In the nonbiting group, significant increases in NA release continued for 80 min after release from stress; however, NA levels in the biting group recovered to basal levels immediately after the cessation of stress. Although many severe gastric lesions with bleeding were found in the nonbiting group, fewer gastric lesions without bleeding were found in the biting group. The cumulative length of gastric lesions in the nonbiting group and in the biting group was 26.2 ± 7.4 and 6.8 ± 3.9 mm (mean ± SEM), respectively. The mean number of ulcers in the nonbiting group and the biting group was 11.8 ± 1.3 and 1.8 ± 0.7 (mean ± SEM), respectively. Both the cumulative length of ulcers and the number of ulcers were significantly lower than those seen in the nonbiting group. These findings strongly suggest that expression of aggression during stress exposure attenuates not only stress-induced increases in NA release in the rat amygdala but also gastric ulcer formation consequent to stress.

Effect of aging on psychological stress-induced increases in noradrenaline release in the rat anterior hypothalamus: an in vivo microdialysis study

Basal and psychological stress-induced noradrenaline (NA) release were studied by intracerebral microdialysis in the hypothalamus of rats aged 9 weeks or 12 months. Basal NA output was not significantly different between young (9-week-old; 2.11±0.22 pg/20 min) and aged (12-month-old; 2.29±0.34 pg/20 min) rats. Psychological stress for 20 min significantly increased NA release in both groups (186% and 142% of baseline at 9 weeks old and 12 months old, respectively); however, the increase in aged rats was significantly lower than that in young rats ( P<0.01). This finding suggests that the noradrenergic neuronal response to psychological stress is attenuated in aged rats.

Involvement of corticotropin-releasing factor in the stress-induced increases in noradrenaline release in rat brain regions

Involvement of corticotropin-releasing factor in the stress-induced increases in noradrenaline release in rat brain regions

Peptidergic mechanisms of resistance to behaviorally evoked emotional stress

Under the various stressful situations, i t has been well known that the monoaminergic neuronal systems including noradrenaline (NA), dopamine (DA) and serotonin (5-hydroxytryptamine, 5-HT) are activated in the extended brain regions of the rodents. Based upon the previous experimental findings, we have proposed the hypothesis on anxiety that increases in NA release in such brain regions as the hypothalamus, amygdala and locus coeruleus are, in part, closed related to the provocation of anxiety and/or fear in animals exposed to stress. Moreover, we have suggested that anxiolyt ic drugs of benzodiazepines act to attenuate stress-induced increases in NA release in these regions, which results in the re l ie f of anxiety and/or fear. Recently, intracerebral microdialysis methods have been ut i l ized in the f ie ld of neurochemistry. In the present studies, we have investigated the effect of emotional stresses on neurotransmitter release such as NA, DA and 5-HT in the rat brain regions using in vivo microdialysis. Male Wistar rats weighing 200-300 g were used. The rats were anesthetized by pentobarbital and the microdialysis probe was inserted into one of the anterior hypothalamus, basolateral nucleus of the amygdala, medial prefrontal cortex, etc.. Perfusion was started 24 hrs after the operation with the flow rate of 2.5 ~I/min. One of NA, DA or 5-HT was determined by HPLC with ECD. Immobilization stress caused signif icant increases in extracelluar NA contents in the perfusates from the anterior hypothalamus and these increases were s igni f icant ly attenuated by diazepam, an anxiolyt ic of benzodiazepines in a flumazenil (an antagonist of benzodiazepines) reversible manner. The same stress increased NA contents from the basolateral nucleus of the amygdala and DA contents from the medial prefrontal cortex but neither from the nucleus accumbens nor from the caudate nucleus. Conditioned fear, wherein the rats were reexposed to the shock box without shock where they had received electr ic shock previously, caused increases in NA contents in the perfusate from the anterior hypothalamus. Psychological stress, wherein the rats were never shocked but exposed to the emotional responses shown by other electrically-shocked rats, increased 5-HT release in the medial prefrontal cortex and the basolateral nucleus of the amygdala. These findings further support our NA hypothesis on anxiety, however, involvements of other brain regions such as the medial prefrontal cortex and other monoamnergic systems including DA and 5-HT systems, are also important for the provocation of anxiety and/or fear.

Psychological stress-induced increases in noradrenaline release in rat brain regions are attenuated by diazepam, but not by morphine

By measuring levels of noradrenaline (NA) and its major metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO 4) in the hypothalamus, amygdala and locus coeruleus region, we investigated the effects of diazepam 5.0 mg/kg, morphine 6.0 mg/kg, or naloxone at 5.0 or 10 mg/kg injected SC immediately before stress exposure, on increases in NA release caused by psychological stress. Psychological stress, wherein rats were exposed to emotional responses which were displayed by other electrically shocked rats, significantly increased MHPG-SO 4 levels in the three brain regions examined and elevated plasma corticosterone levels. Both increases in brain MHPG-SO 4 levels and elevations of plasma corticosterone levels induced by stress were attenuated significantly by diazepam but neither by morphine nor by naloxone. MHPG-SO 4 levels in the hypothalamus and amygdala in the morphine-stress group were significantly higher than those in the saline-stress group. These findings suggest that psychological stress, in which an emotional factor is predominantly involved, causes increases in NA release in these brain regions examined and that these increases are attenuated only by diazepam, in contrast to the previous report, where increases in brain NA release caused by immobilization stress are attenuated not only by diazepam but also by morphine and and enhanced by naloxone.

Pentobarbital attenuates stress-induced increasesin noradrenaline release in specific brain regions of rats

To examine whether anxiolytic action of drugs acting at the GABA/BZD-chloride channel complex may be related to the brain noradrenergic system, we investigated the effect of pentobarbital, a typical barbiturate which has potent GABA modulating properties, on increased NA release in nine brain regions of stressed rats. Pentobarbital (10 and 25 mg/kg) was injected IP 65 min before sacrifice (5 min before one-hour immobilization stress). Levels of 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO 4), the major metabolite of brain noradrenaline (NA), and of plasma corticosterone, were fluorometrically determined. Pentobarbital treatment by itself increased MHPG-SO 4 levels in the thalamus, locus coeruleus (LC) region, midbrain and basal ganglia of nonstressed rats. Stress produced increases in MHPG-SO 4 levels in all brain regions examined and elevation of plasma corticosterone levels. Pentobarbital attenuated, in a dose-dependent manner, stress-induced increases in MHPG-SO 4 levels in the hypothalamus, thalamus, anterior cerebral cortex, LC region and basal ganglia and also attenuated the stress-induced elevation of plasma corticosterone levels. These data suggest that pentobarbital can attenuate both stress-induced increases in NA release in specific brain regions as well as activation of the hypothalamo-pituitary-adrenocortical system. These attenuating effects may be related to the anxiolytic action of barbiturates.

O-247 - The attenuating effect of diazepam on stress-induced increases in noradrenaline release in rat brain regions varies according to the time of diazepam administration

O-247 - The attenuating effect of diazepam on stress-induced increases in noradrenaline release in rat brain regions varies according to the time of diazepam administration

O-248 - Stress-induced increases in noradrenaline release in the rat hypothalamus assessed by intracranial microdialysis method

O-248 - Stress-induced increases in noradrenaline release in the rat hypothalamus assessed by intracranial microdialysis method

Met-enkephalin, injected during the early phase of stress, attenuates stress-induced increases in noradrenaline release in rat brain regions

By measuring levels of 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO 4), the major metabolite of noradrenaline (NA), we investigated the effects of Met-enkephalin (Met-ENK) ICV injected at three different stages of stress, i.e., 0 min, 5 min, or 10 min after exposure to immobilization stress. Immobilization stress caused significant increases in MHPG-SO 4 levels in all brain regions examined, i.e., the hypothalamus, amygdala, thalamus, midbrain, hippocampus and locus coeruleus (LC), which suggests that stress increases NA release in these regions. Met-ENK at a dose of 50 μg, injected ICV immediately before stress exposure significantly attenuated stress-induced increases in MHPG-SO 4 in the amygdala, thalamus and LC, but did not have such an effect when injected either 5 min or 10 min after exposure to stress. Similarly, Met-ENK at 150 μg, injected at 0 min significantly attenuated these increases in all brain regions examined, however, it did not do so when given at 5 min or 10 min after stress initiation. The amount of defecation and the weight loss caused by stress were also significantly attenuated by Met-ENK injected but only at 0 min. These results suggest that the attenuating effect of Met-ENK on stress-induced increases in NA release is greatly affected by the time of the peptide administration and that Met-ENK might inhibit stress-induced increases in NA release in these regions by affecting the initial changes induced by stress.

Naloxone, given before but not after stress exposure, enhances stress-induced increases in regional brain noradrenaline release

Male Wistar rats were injected with either saline or naloxone at a dose of 5 mg/kg either 10 min before exposure to a 1-hour period of immobilization stress or after exposure to the same stress for 2 hours which was then followed by a further 1-hour stress exposure (a total of 3 hours of immobilization stress). Levels of noradrenaline (NA) and its major metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO 4) in six discrete brain regions were determined fluorometrically. Both one hour and three hours of immobilization stress significantly increased MHPG-SO 4 levels in all brain regions examined. This effect was accompanied by significant reductions of NA levels excluding the cerebral cortex after 1 hour of stress. Naloxone, injected prior to stress exposure, significantly enhanced MHPG-SO 4 increases in the hypothalamus, amygdala and thalamus, but did not do so when injected 2 hours after stress exposure. Naloxone administration at either time did not affect stress-induced increases in MHPG-SO 4 levels in the hippocampus, cerebral cortex or pons plus medulla oblongata. These results suggest that naloxone enhances stress-induced increases in NA release in the hypothalamus, amygdala and thalamus only during the early period of immobilization stress. Furthermore, these findings suggest that endogenous opioid peptides might be preferentially released during the initial exposure to stress.

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-SO 4), 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-SO 4 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.