Ulcerogenic effect of a GABA derivative, baclofen, in the rat: Effect of hypothermia.

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Abstract
The ulcerogenic action of baclofen, a lipophilic derivative of GABA, was studied in the urethane anesthetized rat in relation to body temperature. Baclofen at the doses of 2, 4 and 8 mg/kg, s.c. induced gastric ulceration in a dose-dependent manner in the hypothermic (body temperature: 28 .apprx. 30.degree. C) rat. Duodenal ulcers were also observed in about 80% of the hypothermic animals treated with the highest dose of baclofen. Baclofen, even at 8 mg/kg s.c., however, failed to induce gastric ulceration in the normothermic (body temperature: 37 .apprx. 38.degree. C) rat. Histamine, at the secretagogue dose causing acid secretion as potently as 8 mg/kg of baclofen, induced gastric ulcers in both the hypothermic and the normothermic rats. These results indicate that the ulcerogenic effect of baclofen is closely related to the thermoregulation mechanism and may provide important clues for clarifying the pathophysiology of gastroduodenal ulcers induced by hypothermic treatments such as water-immersion stress ulcers or cold exposure ulcers.