Effect of bromazepam on stress-induced gastric ulcer in rats and its relation to brain neurotransmitters.
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.
Saad
S F
SF
Department of Pharmacology, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, Egypt. azzaagha@hotmail.com
Agha
A M
AM
Amrin
A el-N
Ael-N
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
D000897:Anti-Ulcer Agents; D018757:GABA Modulators; D006023:Glycoproteins; D018377:Neurotransmitter Agents; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D004298:Dopamine; D001960:Bromazepam; D009638:Norepinephrine