Gastric mucosal erosions induced by lateral hypothalamic damage: neuronal and dopaminergic mechanisms.
Electrolytic lateral hypothalamic (LH) lesions produce numerous disorders including aphagia, gastric mucosal erosions and autonomic and sensorimotor dysfunctions. This series of experiments examined whether damage to LH neurons or dopaminergic fibers of passage produce similar forms and severity of gastric erosions, as well as other disorders. In Experiment 1, LH neurons were destroyed by the excitatory neurotoxin, kainic acid, that presumably leaves axonal fibers of passage intact. Relatively selective damage to LH neurons with kainic acid produced glandular gastric erosions, as well as sensorimotor and autonomic dysfunctions similar to those seen following electrolytic LH lesions. This suggests that direct damage to LH cell bodies may be a primary cause of many of the disorders observed following LH lesions. In Experiments 2 and 3, electrolytic lesions were used to destroy cell bodies in the substantia nigra and their dopaminergic fibers (some of which pass through the LH area). This resulted in the production of gastric erosions in the absence of significant autonomic dysfunctions. Furthermore, atropine methylnitrate prevented the occurrence of gastric erosions following substantia nigra lesions, suggesting that the erosion formation is mediated via parasympathetic-vagal activity. In contrast, destruction of the ventral tegmental area (and its associated dopaminergic fibers) had no significant effect on gastric erosion formation. Experiment 4 showed that apomorphine, a central and peripheral dopamine agonist, provided protection against LH lesion-induced gastric erosion formation, whereas domperidone, a peripheral dopamine antagonist, had no effect. Taken together, this study suggests that (a) both LH neurons and fibers of passage provide a potential anatomical basis for the development of gastric mucosal erosions, (b) that an alteration in dopamine levels, either centrally or peripherally, may represent an important neurochemical mechanism for the development of erosions, and (c) that the occurrence of gastric erosion can be dissociated from other symptoms of the LH syndrome.
Roland
B L
BL
Department of Psychology and Brain Research Institute, University of California, Los Angeles 90024.
Grijalva
C V
CV
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D004294:Domperidone / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D015259:Dopamine Agents / Q000494:pharmacology; D018492:Dopamine Antagonists; D005753:Gastric Mucosa / Q000473:pathology*; D007026:Hypothalamic Area, Lateral / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D007608:Kainic Acid; D008297:Male; D009412:Nerve Fibers / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013238:Stereotaxic Techniques; D013378:Substantia Nigra / Q000033:anatomy & histology / Q000502:physiology; D013681:Tegmentum Mesencephali / Q000033:anatomy & histology / Q000502:physiology
D015259:Dopamine Agents; D018492:Dopamine Antagonists; D004294:Domperidone; D001285:Atropine; D001058:Apomorphine; D007608:Kainic Acid; D004298:Dopamine