Stress Ulcer Formation In Rats Research Articles

Protective effect of polyunsaturated phosphatidylcholine pretreatment on stress ulcer formation in rats

Purpose The aim of this study was to investigate whether polyunsaturated phosphatidylcholine. (PPC) pretreatment has any protective effect on gastric mucosal damage induced by cold-restraint stress (CRS) in rats. Methods Forty swiss albino rats were divided into 3 groups. Group 1 (n = 10) was control, group 2 (n = 15) was stress ulcer, and group 3 (n = 15) was PPC-treated rats with stress ulcer. Stress ulcer was induced by the cold-restraint method for 4 hours at 4°C after a starvation period of 72 hours. In the group 3 rats, PPC treatment was started 10 days before stress at a dose of 100 mg/d by oral route. Rats were terminated, stomachs were excised. Macroscopic ulcer index (UI), gastric tissue malondialdehyde (MDA) and superoxide dismutase (SOD) activities, plasma total nitrite, and erythrocyte catalase (CAT) concentrations were assayed. Results Histopathologic examination showed a stress ulcer index of 0.12 ± 0.19 mm in the treatment group and 23.6 ± 8.97 mm in the stress ulcer group ( P < .001). Tissue MDA and SOD concentrations were higher in the stress ulcer group than in the treatment group, the differences were statistically significant ( P < .001). Plasma NO 3 −+ NO 2 − levels were higher ( P< .005) and CAT levels were lower ( P < .001) in the nontreatment group. There were no significant differences with respect to Ul, MDA, and SOD levels among the control and treatment groups ( P > .05). Conclusions These results suggest that pretreating rats with PPC inhibits cold-restraint stress-induced gastric mucosal injury and might be useful in preventing stress-induced stomach ulcers.

The role of paraventricular nucleus of hypothalamus in stress-ulcer formation in rats

The rat stress model of restraint and cold water immersion was used to investigate the effect of stimulating the paraventricular nucleus (PVN) of hypothalamus on the development of stress-induced gastric ulceration. The results were (1) electric stimulation of the PVN increased the stress ulceration, while electrolytic lesion of the PVN decreased ot' (2) intracerebroventricular injection (i.e.v.) of acetylcholine (Ach) enhanced the effect of PVN stimulation on stress ulcers, and the M-receptor was involved; (3) i.c.v. norepinephrine (NE) attenuated the effect of PVN stimulation on stress ulcers in a dose-dependent manner, and the β-receptor was involved; (4) i.c.v. 5-hydroxtryptamine (5-HT) enhanced the effect of PVN stimulation on stress ulcers; (5) electrolytic lesions of dorsal raphe nucleus (DR) attenuated the effect of PVN stimulation on stress ulcers, while electrolytic lesions of the locus ceruleus (LC) aggravated the effect; (6) thyroidectomy, adrenalectomy, ovariectomy, vagotomy and sympathectomy all attenuated the effect of PVN stimulation on stress ulcers; (7) electric stimulation of the PVN produced no effect on gastric juice volume, acidity, total acid output, pepsin activity or the gastric barrier mucus; but greatly reduced gastric mucosal blood flow. These results indicate that the PVN is an important brain site regulating the development of stress-induced gastric ulcers, that the classical neurotransmitters Ach, NE and 5-HT are involved, and that in the periphery, both the parasympathetic and sympathetic nervous systems and the three endocrine glands (thyroid, adrenal and gonad) take part in the effect.

A differential dopamine receptor involvement during stress ulcer formation in rats

The involvement of dopaminergic (DA) receptors and their possible interactions were evaluated during stress ulcer formation in rats. The DA 1 antagonist SCH 23390 (0.025, 0.05, or 0.1 mg/kg) produced only marginal aggravations in gastric stress pathology when compared to vehicle controls. The DA 2 antagonist sulpiride (10 or 50 mg/kg) had dose-related effects. The lower dose aggrevated whereas the higher dose attenuated stress ulcerogenesis. The DA 2 agonist bromocryptine (2.5 or 5.0 mg/kg), however, attenuated gastric stress ulcers. Pretreatment of rats with the DA depletor α-methyl-para-tyrosine or the DA 1-antagonist SCH23390 clearly neutralized the stress ulcer-attenuating effects of bromocryptine. These results reaffirm a gastric cytoprotective role for DA and further suggest that DA 1-DA 2 receptor interactions are crucial during DAergic regulation of gastric mucosal integrity during stress.

The basolateral amygdala, dopamine and gastric stress ulcer formation in rats

Bilateral microinjections of dopamine (DA, 0.3, 3.0 or 30.0 μg) or the DAagonist, bromocryptine (3.0 μg) into the basolateral amygdala (BLA) dose-dependently attenuated cold restraint stress (3 h at 4 °C) -induced gastric ulcer formation in rats. On the other hand, intra-BLA injections of the neurotoxin, 6-hydroxydopamine (10 μg) or the DA-antagonist, haloperidol (0.1 or 1.0 μg) aggravated such stress ulcer formation. All these effects were seen only when the injection sites were localized in the posterior (and not the anterior) BLA. Further, pretreatment of rats with haloperidol (0.1 μg) clearly antagonized the gastric cytoprotective effects of DA or bromocryptine (both at 3.0 μg), when both chemicals were injected in the posterior BLA. The results indicate that DA-ergic mechanisms in the posterior BLA are important for the regulation of gastric mucosal integrity during cold restraint stress.

TRH-enkephalin interactions in the amygdaloid complex during gastric stress ulcer formation in rats

The formation of gastric stress ulcers was studied as a function of interactions between thyrotropin releasing hormone (TRH) and endogenous opioids in the central amygdalar nucleus (CEA) in rats. Bilateral microinjections of TRH (1 or 10 μg) into the CEA produced dose-related aggravations in cold restraint stress (CRS, 3 h at 4°C) — induced gastric ulcer formation. Similar stress ulcer facilitating effects were also seen with intra-CEA injections of the opioid antagonist, naloxone (1 or 10 μg). On the other hand, the enkephalin analog, d-Ala 2-metenkephalinamide (DAMEA, 1, 10 or 20 μg) produced dose-dependent attenuations in gastric stress pathology, the effects being most marked with the latter two doses. Pretreatment of rats with intra-CEA naloxone (1 μg) (a) antagonized the gastric cytoprotective effects of DAMEA (20 μg) and (b) further aggravated the ulcerogenic response of TRH (1 μg), without influencing significantly the TRH (10 μg) effect. Further, when DAMEA (20 μg) was administered intra-CEA just after TRH (10 μg), the stress ulcer facilitating effects of the latter was neutralized. The results indicate that TRH-enkephalin interactions are possible at the level of the CEA during CRS-induced gastric ulcer formation.

Effects of intra-amygdalar Thyrotropin Releasing Hormone (TRH) and its antagonism by atropine and benzodiazepines during stress ulcer formation in rats

Bilateral intra-amygdalar (i/am) microinjections of TRH (1 and 10 μg) and physostigmine (10 μg) into the central nucleus (CEA) aggravated cold restraint stress (3 hr at 4°C) induced gastric ulcer formation in rats, whereas atropine (1, 5 and 10 μg) attenuated this phenomenon. Similar stress ulcer reducing effects were seen with chlordiazepoxide (CDP, 10 mg/kg, IP) and midazolam (1, 3 and 10 μg, i/am). Pretreatment of rats with atropine or CDP antagonized the ulcerogenic effects of both TRH and physostigmine. Further, when administered intra-CEA, midazolam neutralized the effects of TRH in a dose-related manner. These results are discussed in light of TRH-acetylcholine-benzodiazepine/GABA interactions within the amygdaloid complex during stress ulcer formation.

Noradrenergic mechanisms in the central amygdalar nucleus and gastric stress ulcer formation in rats

Microinjections of noradrenaline (NA, 0.3, 3.0 and 30.0 μg) into the central amygdalar nucleus (CEA) produced dose-related attenuations of cold restraint (3 h at 4°C) induced gastric ulcer formation in rats. On the other hand, stress ulcer aggravating effects were seen with β-adrenoceptor antagonist, propranolol (10 μg) but not with the α-adrenoceptor antagonist, prazosin (1 and 10 μg). Moderate enhancements of gastric stress lesions were also seen with the NA release inhibitor clonidine (1 μg) and the neurotoxin DSP-4 (25 μg). Further, pretreatment of rats with intra-amygdalar (i.am.) propranolol but not prazosin, antagonized and reversed the gastric cytoprotective effects of NA. The results indicate that β-adrenoceptor-mediated NAergic mechanisms at the level of the CEA are important for the maintenance of gastric mucosal integrity during immobilization stress.

Enkephalin-dopamine interactions in the central amygdalar nucleus during gastric stress ulcer formation in rats

Intra-amygdalar (i/am) microinjections of the enkephalin analog, ( d-Ala 2)-Met-enkephalinamide (DAMEA, 3, 10 and 30 μg) into the central amygdalar nucleus (CEA) produced a dose-related, naltrexone-reversible attenuation of cold restraint (3 h at 4°C)-induced gastric mucosal lesions in rats. Similarly, gastric stress ulcer formation was also inhibited by i/am dopamine (DA, 10 μg) - an effect which was reversed by the DA-antagonist, clozapine (5 mg/kg) pretreatment. Further, pretreatment of rats with clozapine or the DA-neurotoxin, 6-hydroxydopamine (6-OHDA, 10 μg, i/am) clearly reversed and/or antagonized the gastric cytoprotective effect of DAMEA (30 μg). The results indicate interactions between enkephalinergic and DAergic systems at the level of the CEA in the maintenance of gastric mucosal integrity during immobilization stress.

Influence of aging on stress ulcer formation in rats.

The effects of aging on stress ulcer formation were examined in male Fischer 344 rats at 2, 8-9, 11-12, 17-18 and 21-24 months old. The animals were restrained and immersed in a water bath (22 degrees C) for 1, 2, 4 and 8 h. The incidence and severity of gastric corpus ulceration increased linearly with age. Basal acid secretion, determined 4 h after pylorus ligation, decreased with age, but there were no age-related differences in the effect on acid secretion of histamine and vagal nerve stimulation in the lumen-perfused stomachs of anesthetized rats. On morphological examination, surface epithelial cells in aged rats (21-24 months) were found to be intact, but the gastric foveolae were shallow and the chief cell layer was thick in aged rats. Deficiencies of vascular networks were observed in aged rat stomachs. These results indicate that an insufficiency of gastric mucosal microvascular networks and the preserved gastric acid response in the vulnerable mucosa may be involved in the mechanisms underlying aggravation of stress ulcer formation in aged rats.

The effects of buspirone, a selective anxiolytic, on stress ulcer formation in rats

The effects of buspirone hydrochloride were investigated in the formation of cold-immobilization gastric stress ulcers. Low doses significantly attenuated, while higher doses greatly potentiated gastric stress pathology. The dopamine antagonist haloperidol, and the agonist apomorphine respectively, reversed the buspirone effects. The role of dopamine in the expression of buspirone's effects is discussed, although other transmitter systems may mediate some of the actions of buspirone.

Interactions of thyrotropin-releasing hormone (TRH) with neurotensin and dopamine in the central nucleus of the amygdala during stress ulcer formation in rats

Bilateral microinjections of thyrotropin-releasing hormone (TRH; 1, 3 and 10 μg) into the central nucleus of the amygdala produced a dose-related aggravation of cold restraint-induced gastric ulcers in rats. TRH (10 μg) also induced gastric erosions in non-stressed animals. Pretreatment with atropine methyl nitrate attenuated the TRH-induced ulcers in both stress and non-stress situations. TRH (10 μg) also antagonized the gastric cytoprotection of intra-amygdalar neurotensin (10 μg) and was ineffective in altering the stress ulcer-attenuating effects of dopamine (10 μg). Pretreatment with i.p. clozapine, however, prevented the inhibitory effects of dopamine on the TRH-induced aggravation of the gastric stress pathology. The results suggest an interaction of TRH, neurotensin and dopamine in the central amygdalar nucleus during stress, and indicate peripheral cholinergic pathways in the mediation of the ulcerogenic effects of TRH.

The effects of environmental enrichment on voluntary ethanol consumption and stress ulcer formation in rats

The effects of exposure to an enriched environment on subsequent voluntary ethanol intake and response to restraint stress were examined. Rats at 21 days of age were reared in an enriched environment for 90 days. Non-enriched animals were reared individually in standard laboratory cages. Following an initial 36 day ethanol exposure period, voluntary ethanol (9% v/v) preference was assessed for 10 days. In addition, at the conclusion of the ethanol test session, animals were exposed to restraint stress for a 3 hr period. Results indicate that exposure to an enriched environment produces increased voluntary ethanol consumption as compared to non-enriched controls. Furthermore, animals reared in the enriched environment demonstrated reduced gastric ulcer severity in response to restraint stress. Ethanol per se did not affect ulcer formation.

A simplified restraint technique to study the effect of enteral feeding in the control of stress ulcer formation in rats : [formula omitted] Midwest Nutrition. Ed.& Res. Found.& Dept.of Surg., Univ. of Health Sciences, Chicago Med.School, Chicago, Illinois, USA

A simplified restraint technique to study the effect of enteral feeding in the control of stress ulcer formation in rats : [formula omitted] Midwest Nutrition. Ed.& Res. Found.& Dept.of Surg., Univ. of Health Sciences, Chicago Med.School, Chicago, Illinois, USA