Pentobarbital attenuates stress-induced increases in 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-SO4), the major metabolite of brain noradrenaline (NA), and of plasma corticosterone, were fluorometrically determined. Pentobarbital treatment by itself increased MHPG-SO4 levels in the thalamus, locus coeruleus (LC) region, midbrain and basal ganglia of nonstressed rats. Stress produced increases in MHPG-SO4 levels in all brain regions examined and elevation of plasma corticosterone levels. Pentobarbital attenuated, in a dose-dependent manner, stress-induced increases in MHPG-SO4 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.     

Effects of neurotropin on regional brain noradrenaline metabolism in rats

By measuring levels of noradrenaline (NA) and its major metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO4), in various rat brain regions, we investigated the effects of an extract isolated from vaccinia virus-inoculated and inflamed skin or tissue of rabbits (Neurotropin, NSP), administered acutely or chronically, on regional NA metabolism in stressed and nonstressed rats. An acute administration of NSP at 50 mg/kg significantly elevated MHPG-SO4 levels in the amygdala and cerebral cortex; and 100 mg/kg of the drug significantly increased the metabolite levels in the hypothalamus, amygdala, thalamus, midbrain, cerebral cortex and pons plus medulla oblongata without affecting NA levels. This suggests that acutely injected NSP slightly increases NA release in these brain regions. One hour immobilization stress caused significant increases in MHPG-SO4 levels, which were not affected by pretreatment with either 50 mg/kg or 100 mg/kg of NSP. Chronic injection with NSP daily at either 50 mg/kg or 100 mg/kg for 7 days was without effect on NA metabolism in all brain regions examined. However, increases in MHPG-SO4 levels caused by stress were significantly attenuated in some regions including the hypothalamus, amygdala and midbrain in chronic NSP-treated rats. This indicates that although an acute administration of NSP slightly increases brain NA release, a chronic treatment with NSP rather attenuates increases in NA release caused by immobilization stress in brain regions such as the hypothalamus, amygdala and midbrain. This suggests a possibility that these attenuating effects on stress-induced increases in brain NA release caused by chronic administration of NSP might be related to the stress-reducing or anti-stress properties of NSP.     

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-SO4) 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-SO4 levels in the three brain regions examined and elevated plasma corticosterone levels. Both increases in brain MHPG-SO4 levels and elevations of plasma corticosterone levels induced by stress were attenuated significantly by diazepam but neither by morphine nor by naloxone. MHPG-SO4 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 are enhanced by naloxone.     

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-SO4), 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-SO4 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 micrograms, injected ICV immediately before stress exposure significantly attenuated stress-induced increases in MHPG-SO4 in the amygdala, thalamus and LC, but did not have such an effect when injected either 5 min or 10 min or 10 min after exposure to stress. Similarly, Met-ENK at 150 micrograms 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.     

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 animal's 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.     

Stressor predictability and rat brain noradrenaline metabolism

This study examined the effects of stressor predictability on regional rat brain noradrenaline (NA) turnover, by measuring levels of a principal metabolite of NA (3-methoxy-4-hydroxyphenylethyleneglycol sulfate, MHPG-SO4). Male Wistar rats were exposed to one of three shock conditions for 19 hr: nonshock, signalled, and unsignalled shocks. Rats in the shock conditions received shock (1.2 mA intensity, 2 sec duration) on a 2.5 min variable time (VT) either preceded by a 12-sec, 10-W light signal (signal-shock interval of 10 sec) or not preceded by this signal. The tail electrodes for these rats were in series, so that the shock received by all rats was of exactly the same number and duration. After 19 hr in a VT-2.5 min shock session, the rats exposed to unsignalled shock (unpredictable group) showed significantly greater increases in MHPG-SO4 levels in the hypothalamus, amygdala, midbrain, cerebral cortex, thalamus and locus coeruleus, as well as in plasma corticosterone levels. Rats exposed to signalled shock (predictable group) showed significant increases in MHPG-SO4 levels in the first four of these regions, as compared to the nonshocked rats. Moreover, the unpredictably shocked rats exhibited greater elevations in MHPG-SO4 levels in the hypothalamus, amygdala, and thalamus, as well as in plasma corticosterone levels, when compared to the predictably shocked rats. These results are consistent with previous reports showing that unsignalled shock induced extensive somatic effects in comparison to signalled shock. The present study suggests that the presence of a signal attenuates the extent of NA release in some brain regions resulting from irregular inescapable shock stress.     

Differential modification by opioid agents of acutely enhanced noradrenaline release in discrete brain regions

Although immobilization stress-induced increases in MHPG-SO4 level in the hypothalamus, amygdala and thalamus were enhanced by naloxone and attenuated by morphine, both agents failed to exert significant effects upon regional MHPG-SO4 levels in methamphetamine-treated rats. The results indicate that there is a differential modification by opioid agents of acutely enhanced noradrenaline release induced by physiological and by pharmacological manipulations.     

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 of 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.     

Differential effects of ethanol on plasma catecholamine levels in rats

Acute ethanol administration (1-4 g/kg, i.p.) had no effect on plasma catecholamine levels in nonstressed animals except at the highest dose where levels of both catecholamines increased. In animals stressed for 30 min, the higher doses had a biphasic effect on plasma catecholamines; at earlier times during stress a reduction in stress-induced increases in both catecholamines was seen, whereas later during stress or after release from stress an increase was noted. Semi-chronic ethanol administration (0.5 and 2 g/kg/day, i.p.) had no significant effect on plasma catecholamine levels in nonstressed rats. In stressed rats, ethanol reduced stress-induced catecholamine increases but these reductions were less than those seen after acute administration. Although ethanol reduced the gross behavioral stress response, no correlation between gross behavioral and biochemical responses was detected. These data show that ethanol can indeed reduce the behavioral and biochemical stress responses in rats but that effects seen depend on the state (nonstressed vs stressed) of the animal, the dose of ethanol (low vs high) used, the length of ethanol administration (acute vs semi-chronic), and the time of measurement of the catecholamine level after ethanol administration.     

Behavioral and neurochemical changes in response to acute stressors: influence of previous chronic exposure to immobilization.

The effect of daily (2 h) exposure to immobilization (IMO) for 15 days on the behavioral and neurochemical responses of adult male rats to acute stress caused by 2-h IMO or 2-h tail-shock was studied. The brain areas studied were frontal cortex, hippocampus, hypothalamus, midbrain, and pons plus medulla. Chronic exposure to IMO did not alter noradrenaline (NA), 3-methoxy,4-hydroxyphenyletileneglycol-SO4 (MHPG-SO4), serotonin, or 5-hydroxindoleacetic acid (5-HIAA) concentrations in any brain area as measured approximately 20 h after the last exposure to IMO. Exposure to behavioral tests did not modify neurochemical variables except NA levels in the hypothalamus of nonchronically stressed (control) rats. Both exposure to 2-h IMO or 2-h shock significantly decreased NA levels in hypothalamus and midbrain of nonchronically stressed rats. These decreases in response to the two acute stressors were not observed in chronically stressed rats. However, MHPG-SO4 levels increased to the same extent in control and chronically stressed rats after exposure to the acute stressors. Likewise, increased 5-HIAA concentrations observed in response to acute stressors were similar in control and chronically stressed rats. The inhibition of activity (areas crossed and rearing) in the holeboard caused by acute IMO was less marked in rats previously exposed to the same stressor than in control rats, but the response to shock was similar. In the forced swim test, acute IMO decreased struggling in control rats but tended to increase it in chronically stressed rats. The response to shock followed the same pattern as that to IMO, although it was slight.(ABSTRACT TRUNCATED AT 250 WORDS)     

Methylphenidate effects on activity-stress gastric lesions and regional brain noradrenaline metabolism in rats

Methylphenidate (5, 10, or 20 mg/kg/day) or saline were administered to rats in the activity-stress ulcer paradigm. Running-wheel activity and food consumption did not differ among groups. Methylphenidate produced dose-related increases in gastric ulcer severity, decreases in hypothalamic noradrenaline (NA) and increases in 3-methoxy-4-hydroxy-phenylethyleneglycol sulfate (MHPG-SO4) in the hypothalamus, amygdala, hippocampus and thalamus. These results differ markedly from the effects seen with a related substance, d-amphetamine, and suggest different mechanisms of action for these drugs.     

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 regionsrespond differentially to stress and reflect their own characteristic patterns depending upon nature and time-course of the stressor.     

Effect of ethanol on plasma amino acids and related compounds of stressed male rats

Plasma amino acid levels in rats are known to be affected by ethanol or by immobilization stress. This paper investigated the effect of ethanol on plasma amino acid levels of stressed rats. Rats received ethanol (2 g/kg, IP) 15 minutes prior to a 30-min immobilization period. Blood samples were obtained from individual rats before, during and after stress. Ethanol lowered the concentration of most plasma amino acids (AA) or related compounds in stressed rats (e.g., aspartic acid, threonine, serine, glycine, alanine, valine, tyrosine, phenylalanine, tryptophan). Some compounds remained unaffected (e.g., taurine, cystine, ethanolamine and methylhistidines) and one (phosphoethanolamine) increased initially. A comparison of the effects of ethanol on plasma AA and related compounds in resting and stressed rats shows similarities and differences. In general, ethanol tends to change the concentrations of these compounds away from normal levels in nonstressed rats, whereas in stressed rats, ethanol tends to antagonize stress-induced changes. This study shows that ethanol can affect individual AA and related compounds differently in nonstressed and stressed rats and that ethanol reduces stress-induced changes. The latter finding supports the "tension-reduction hypothesis" of ethanol.     

Anxiogenic beta-carboline FG 7142 produces activation of noradrenergic neurons in specific brain regions of rats.

By measuring the levels of two major metabolites of rat brain noradrenaline (NA), 3-methoxy-4-hydroxyphenylglycol (MHPG) and 3,4-dihydroxyphenylglycol (DHPG), we investigated the effects of anxiogenic beta-carboline FG 7142, an inverse agonist of benzodiazepine (BZD) receptors, on brain noradrenergic activity of rats. Thirty min after treatment with FG 7142 (15 mg/kg IP), levels of both MHPG and DHPG in the hypothalamus, amygdala and thalamus, but not in the hippocampus and cerebral cortex, significantly increased. These increases were significantly antagonized by pretreatment with BZD receptor antagonist Ro 15-1788 (15 mg/kg, IP). Sixty min after treatment with FG 7142 at the same dose, significant increases in both metabolite levels occurred in the hypothalamus, amygdala, thalamus and cerebral cortex, and increases in MHPG levels only were observed in the hippocampus. These increases were significantly blocked by pretreatment with alpha 2-adrenoreceptor agonist clonidine (100 microgram/kg, IP). The present findings suggest that FG 7142 can produce increases in brain noradrenergic activity in specific brain regions by interacting with BZD receptors, and may support the hypothesis that hyperactivity of brain noradrenergic systems may be one neural mechanism in provocation of aversive emotional changes (anxiety, fear or panic).     

Protective effect of eugenol against restraint stress-induced gastrointestinal dysfunction: Potential use in irritable bowel syndrome

Abstract

Context: Eugenol, an essential constituent found in plants such as Eugenia caryophyllata Thunb. (Myrtaceae) is reported to possess neuroprotective and anti-stress activities. These activities can potentially be useful in the treatment of stress-induced irritable bowel syndrome (IBS).

Objective: The protective effect of eugenol was assessed against restraint stress (RS)-induced IBS-like gastrointestinal dysfunction in rats. Further, its centrally mediated effect was evaluated in this model.

Materials and methods: Eugenol (12.5, 25, and 50?mg/kg), ondansetron (4.0?mg/kg, p.o.), and vehicle were administered to rats for 7 consecutive days before exposure to 1?h RS. One control group was not exposed to RS-induction. The effect of eugenol (50?mg/kg) with and without RS exposure was evaluated for mechanism of action and per se effect, respectively. The hypothalamic–pituitary–adrenal cortex (HPA)-axis function was evaluated by estimating the plasma corticosterone level. The levels of brain monoamines, namely serotonin, norepinephrine, dopamine, and their metabolites were estimated in stress-responsive regions such as hippocampus, hypothalamus, pre-frontal cortex (PFC), and amygdala. Oxidative damage and antioxidant defenses were also assessed in brain regions.

Results: Eugenol (50?mg/kg) reduced 80% of RS-induced increase in fecal pellets similar to that of ondansetron. Eugenol attenuated 80% of stress-induced increase in plasma corticosterone and modulated the serotonergic system in the PFC and amygdala. Eugenol attenuated stress-induced changes in norepinephrine and potentiated the antioxidant defense system in all brain regions.

Conclusion: Eugenol protected against RS-induced development of IBS-like gastrointestinal dysfunction through modulation of HPA-axis and brain monoaminergic pathways apart from its antioxidant effect.     

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.     

Effects of acute and chronic administration of MCI-225, a new selective noradrenaline reuptake inhibitor with 5-HT3 receptor blocking action, on extracellular noradrenaline levels in the hypothalamus of stressed rats

In the present study, we investigated the effects of acute and chronic systemic administration of MCI-225 (4-(2-fluorophenyl)-6-methyl-2-(1-piperazinyl)thieno[2,3-d]pyrimidine monohydrate hydrochloride), a newly-developed selective noradrenaline (NA) reuptake inhibitor with 5-HT3-receptor-blocking action, on extracellular NA levels in the hypothalamus of stressed and non-stressed rats by utilizing intracerebral microdialysis. Acute administration of MCI-225 (3 and 10 mg/kg, p.o.) significantly and dose-dependently increased extracellular NA levels in the hypothalamus in non-stressed rats. Footshock for 20 min also significantly increased NA levels in the hypothalamus of both groups of rats pretreated with vehicle and MCI-225. Although chronic administration of MCI-225 (3 or 10 mg/kg, p.o. for 14 days) did not alter the basal extracellular NA levels in the hypothalamus, the stress-induced increases in extracellular NA levels were significantly lower in rats chronically treated with MCI-225 (10 mg/kg) than those of rats pretreated with vehicle for the same period. The increase in extracellular NA levels induced by MCI-225 challenge (3 or 10 mg/kg, p.o.) were not different between rats chronically treated with MCI-225 or vehicle. These results suggest that MCI-225 enhances extracellular NA levels in the hypothalamus in both non-stressed and stressed rats by inhibiting NA uptake and that chronic systemic administration of MCI-225 did not alter basal extracellular NA levels, but reduced the increase in NA release caused by footshock stress. These data suggest the possibility that MCI-225 might possess anxiolytic and/or antidepressant properties.     

Daily increase in noradrenaline turnover in brain regions of activity-stressed rats

Changes in contents of noradrenaline (NA) and its major metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO₄) in brain regions (the hypothalamus, amygdala, thalamus, hippocampus, midbrain, cerebral cortex, pons plus medulla oblongata and basal ganglia) of male Wistar rats were evaluated after 1,3 or 5 days of exposure to the activity-stress paradigm, wherein rats were housed in a cage with a running-wheel and restricted to 1-hr of feeding per day. When compared to the non-stressed control rats, contents of MHPG-SO₄ in all the brain regions except of the basal ganglia in the stressed rats increased as rapidly as 1 day and continued to increase throughout the 5-day activity-stress period. Contents of NA did not change significantly in most of these brain regions. The daily increase in regional NA turnover by continuous exposure to the activity-stress paradigm was related to the large increases in running activity and gastric ulcers, and to body weight loss at the 3-day and 5-day testing period. These data suggest that pathological states produced by a 5-day activity-stress paradigm may reflect concomitant disturbances of noradrenergic function in various brain regions. The activity-stress paradigm is regarded as an intense and progressive stress, because it induces an increase in NA response in extended brain regions.     

Effects of buspirone and chlordiazepoxide on plasma catecholamine and corticosterone levels in stressed and nonstressed rats

The effects of intragastric administration of the prototypical benzodiazepine (BDZ) anxiolytic drug chlordiazepoxide (CDP) and the non-BDZ anxiolytic agent buspirone (BUSP) on basal and stress-elevated plasma noradrenaline (NA), adrenaline (A) and corticosterone (CS) contents were investigated. Acute dosing of CDP (1-27 mg/kg) produced dose-related increases in basal CS secretion but was without effect on basal NA levels. The high dose of CDP caused a slight short-term A increase. Dose-dependent increases in plasma A, NA and CS contents were observed after acute treatment with BUSP (2 and 20 mg/kg). A medium dose of CDP (9 mg/kg) attenuated the stress-induced CS and A elevations. High doses of CDP that elevated basal CS release prevented a further increase of CS by stress and inhibited the NA and A response to stress. BUSP (2 and 20 mg/kg) was not effective in decreasing the stress-elicited rise of CS, NA or A. Conversely, the 20 mg/kg dose of BUSP enhanced the stress-induced A response. Repeated administration of CDP (9 mg/kg/day for six days) produced tolerance to the elevation of basal CS triggered by acute CDP treatment, but increased the efficacy of the drug's CS and A attenuating action in stressed rats. Repeated administration of BUSP (2 mg/kg/day for six days) also produced tolerance to the acute BUSP-induced effect on basal CS release, but did not affect the stress-induced CS, NA and A responses. It is concluded that the clinically effective anxiolytic BUSP does not have the BDZ-like property to inhibit stress-induced elevations in CS, NA and A. Furthermore, the present data support other evidence that activation of 5-HT1A receptor mechanisms increases plasma catecholamine and corticosterone concentrations.     

Influence of Momordica charantia on oxidative stress-induced perturbations in brain monoamines and plasma corticosterone in albino rats

Objectives:

The objective of this study was to evaluate the antistress activity of Momordica charantia (MC) fruit extract on stress-induced changes in albino rats and also to explore attenuating effects of MC on in vitro lipid peroxidation in rat brain.

Materials and Methods:

In this study, Wistar albino rats (180–200 g) were used. Plasma corticosterone and monoamines—5-hydroxy tryptamine (5-HT), norepinephrine (NE), epinephrine (E) and dopamine (DA) in cortex, hypothalamus and hippocampus regions of brain were determined in animals under different stressful conditions. Ethanolic fruit extract of MC, at doses of 200 and 400 mg/kg, was used. The oxidative stress paradigms used in in vivo models were acute stress (AS) and chronic unpredictable stress (CUS). Panax quinquefolium (PQ) was used as a standard in in vivo models and ascorbic acid was used as a reference standard in the in vitro method.

Results:

Subjecting the animals to AS (immobilization for 150 min once only) resulted in significant elevation of plasma corticosterone levels and brain monoamine levels. Pretreatment with MC at doses of 200 and 400 mg/kg p.o. significantly countered AS-induced changes and a similar effect was exhibited by PQ at 100 mg/kg p.o. In the CUS regimen (different stressors for 7 days), plasma corticosterone levels were significantly elevated whereas the levels of 5-HT, NE, E, and DA were depleted significantly. Pretreatment with MC (200 and 400 mg/kg) attenuated the CUS-induced changes in the levels of above monoamines in cortex, hypothalamus, and hippocampus regions of brain and plasma corticosterone in a dose-dependent manner. Furthermore, MC extract (1000–5000 μg/mL) exhibited a significant quenching effect on in vitro lipid peroxidation indicating its strong antioxidant activity which was compared with ascorbic acid.

Conclusions:

This study reveals the antistress activity of MC as it significantly reverted the stress-induced changes, and the activity might be attributed to its antioxidant activity since stress is known to involve several oxidative mechanisms.