title: Effect of bromazepam on stress-induced gastric ulcer in rats and its relation to brain neurotransmitters.
abstract: The possible antiulcer potential of bromazepam was investigated in relation to its effect on the levels of central neurotransmitters in rats. Peptic ulcer was induced by cold-restraint stress, by immobilizing the animals in open wire restraint cages placed for 2 h at 4 degrees C. Bromazepam (1 and 2 mg x kg(-1), i.p.) was given as prophylactic regimens, either as a single (2 h before ulcer induction) or repeated (twice daily for 15 days) administration. Results revealed that single (1 mg x kg(-1)) and repeated (1 and 2 mg x kg(-1)) dose regimens of bromazepam succeeded in preventing gastric ulceration, without significant effects on the protein-bound hexose content of gastric mucus. Increases in gamma-aminobutyric acid (GABA) concentrations in almost all tested brain regions were observed in bromazepam-treated groups, as compared to the control stressed group. Cortical dopamine (D) concentrations were reduced following single (2 mg x kg(-1)) as well as repeated administration of bromazepam. Similarly, norepinephrine (NE) concentrations were decreased in the cerebral cortex and thalamus/hypothalamus by repeated doses of bromazepam. Cortical 5-hydroxytryptamine (5-HT) was elevated by single (1 mg x kg(-1)) and repeated (1 mg x kg(-1)) doses of the drug. It could be concluded that bromazepam affords a good gastroprotective potential against cold-restraint stress-induced gastric ulceration and the possible mechanisms might involve an increase in the inhibitory GABA and a suppression of the stimulatory NE and D in central regions, especially the cerebral cortex and/or thalamus/hypothalamus.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, Egypt. azzaagha@hotmail.com
authors.forename: S F
authors.initials: SF
authors.lastname: Saad
authors.forename: A M
authors.initials: AM
authors.lastname: Agha
authors.forename: A el-N
authors.initials: Ael-N
authors.lastname: Amrin
mesh_terms: D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism; D001960:Bromazepam / Q000494:pharmacology*; D003080:Cold Temperature; D019610:Cytoprotection / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D018757:GABA Modulators / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000737:chemistry / Q000187:drug effects; D006023:Glycoproteins / Q000032:analysis; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D010437:Peptic Ulcer / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D013312:Stress, Physiological / Q000150:complications*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000897:Anti-Ulcer Agents; D018757:GABA Modulators; D006023:Glycoproteins; D018377:Neurotransmitter Agents; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D004298:Dopamine; D001960:Bromazepam; D009638:Norepinephrine