Different mechanisms mediated by dopamine D1 and D2 receptors are involved etiologically in activity-stress gastric lesion of the rat.
Rats subjected to activity-stress developed gastric lesions and showed excessive running activity with an increase of light/dark ratio. Daily treatment with centrally acting dopamine antagonists, SCH23390 [(R)-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3- benzazepin-7-ol] (0.1-10 mg/kg), haloperidol (0.1-10 mg/kg), sulpiride (32-320 mg/kg), clozapine (1-100 mg/kg) and metoclopramide (1-100 mg/kg) suppressed the lesion formation: ID50 values were 0.9, 0.4, 53, 8.9 and 60 mg/kg, respectively. On the other hand, domperidone (1-100 mg/kg), a peripherally acting dopamine antagonist, failed to suppress the lesion formation and FR64822 [N-(4-pyridylcarbamoyl)amino 1,2,3,6-tetrahydropyridine] (1-32 mg/kg), a central dopamine enhancer, aggravated it. The excessive running activity was reversed dose-dependently by treatment with haloperidol, a specific dopamine D2 antagonist, but not by SCH23390, a specific dopamine D1 antagonist. Conversely, the increased light/dark ratio was attenuated dose-dependently by SCH23390, but not by haloperidol. Neither antisecretory agents nor 5-hydroxytryptamine antagonists were effective against the lesion formation. These results suggest that an activation of central dopamine D1 and D2 receptors is responsible for the increased light/dark ratio and enhanced running activity, respectively, and that both of the changes are involved in the etiology of activity-stress induced lesions.
Nomura
K
K
Basic Research Group, Tsukuba Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., Ibaraki, Japan.
Maeda
N
N
Yoshino
T
T
Yamaguchi
I
I
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D015738:Famotidine / Q000494:pharmacology; D008297:Male; D009043:Motor Activity; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D013276:Stomach Ulcer / Q000209:etiology*; D013312:Stress, Physiological / Q000150:complications*
D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D015738:Famotidine; D001285:Atropine