Possible prostaglandin-dopamine interactions during experimental gastric ulcer formation

The effects of dopamine (DA) agonists and antagonists were investigated on indomethacin--and restraint stress (6 hr at RT)--induced gastric ulcer formation in rats. The DA-agonists, apomorphine and bromocryptine (both at 5 mg/kg) significantly attenuated the frequency and severity of gastric mucosal lesions in both experimental models. The DA-antagonist, haloperidol (0.05 and 1.0 mg/kg) aggravated the gastric ulcerogenesis of both indomethacin and stress, the effects with the lower dose being statistically significant. Haloperidol (0.05 mg/kg) also prevented the cytoprotective effects of apomorphine on indomethacin-ulcers. The atypical DA-antagonist, sulpiride (10 and 50 mg/kg), however, showed differential dose- and model-specific effects. Whereas, the lower dose attenuated indomethacin-ulcers, the higher dose (50 mg/kg) tended to aggravate this phenomenon. The trend of results were reversed in the restraint stress model. Indomethacin (1 mg/kg) aggravated stress-ulcers, an effect which was also appreciably neutralised by apomorphine (5 mg/kg) pretreatment. These results are discussed in light of possible prostaglandin-DA interactions during such experimental gastric pathology.