Central dopamine involvement in experimental gastrointestinal injury.
1. Rats were prepared with intracerebral cannulas for microinjection of test compounds into various brain regions. 2. Selective dopamine D1 agonists (SKF38393, SKF75670C) and a D1 antagonist (SCH23390) were injected into the cell body regions of the nigrostriatal, mesolimbic and mesocortical dopamine tracts or into a terminal field of these tracts (caudate nucleus, central nucleus of the amygdala and medial prefrontal cortex) prior to gastric ulcer induction by cold-restraint stress or duodenal ulcer induction by cysteamine. 3. The dopamine D1 agonists reduced both stress gastric ulcers and duodenal lesions most significantly when given into either the cell body region or a terminal field of the mesolimbic DA tract with much less effects seen for the nigrostriatal tract. 4. No effects were seen upon infusion of the agonists into the mesocortical cell body or terminal field regions. 5. The D1 antagonist worsened both stress-induced gastric lesions and duodenal lesions if given into mesolimbic regions and, to a much lesser extent when injected into the nigrostriatal tract. 6. No effect of the D1 antagonist was seen upon administration into the mesocortical tract. 7. Central dopamine D1 receptors, particularly in the mesolimbic DA tract, appear to be involved in mediating the gastrointestinal consequences of exposure to stress.
Department of Pharmacology and Therapeutics and Surgery, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
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D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D015259:Dopamine Agents / Q000494:pharmacology; D008024:Ligands; D008297:Male; D010437:Peptic Ulcer / Q000139:chemically induced / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains; D013315:Stress, Psychological / Q000503:physiopathology
D001552:Benzazepines; D015259:Dopamine Agents; D008024:Ligands; C052506:SK&F 75670; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D004298:Dopamine