title: Gyrus cinguli transection abolishes delta-opioid receptor-induced gastroprotection and alters alpha 2 adrenoceptor activity in the lower brainstem in rats.
abstract: Previously, using the acidified ethanol-induced ulcer model in rats, we demonstrated that the mainly vagus-dependent gastroprotective effect of intracerebroventricularly injected clonidine was mediated by beta-endorphin release in the lower brainstem. Presently, retroarcuate transections were used to evaluate the contribution of forebrain beta-endorphinergic projection in this mechanism. Since the transection trajectory affected the cingulate cortex and other forebrain structures, matching lesions were also performed. In control and sham-operated rats intracisternal injection of clonidine and the direct opioid receptor (delta type) stimulant peptide (D-Ala(2), D-Leu(5))-enkephalin caused a potent and fully naloxone-reversible (i.e. opioid receptor-mediated) protection against acidified ethanol-induced mucosal damage. In gyrus cinguli-transected rats (as well as in groups with midline hippocampal, thalamic and hypothalamic lesions) gastric mucosal protection induced centrally by direct delta-opioid receptor stimulation in the lower brainstem was completely abolished. The protective effect of clonidine was significantly reduced but it was still present in these animals. The residual protection by clonidine was naloxone-resistant, i.e. independent of an opioid mediation. Transections of the cingulate gyrus as well as thalamic but not the retroarcuate transections elevated plasma corticosterone levels. The changes seen in the clonidine/opioid-induced gastroprotection did not show any correlation with the changes in plasma corticosterone levels. It was concluded that (i) the transection of the cingulate cortex strongly influences the neural input to the nucleus tractus solitarii-dorsal motor vagal nucleus complex that is required for the activation of gastroprotective vagus outflow by delta-opioid receptor stimulation; (ii) the transection uncovers a direct, clonidine-induced gastroprotective pathway which is probably suppressed in intact animals.
authors.affiliation: Semmelweis University Faculty of Medicine, Department of Pharmacology and Pharmacotherapy; H-1445, POB 370, Budapest, Hungary. ronand@pharma.sote.hu
authors.forename: András Z
authors.initials: AZ
authors.lastname: Rónai
authors.forename: Klara
authors.initials: K
authors.lastname: Gyires
authors.forename: István
authors.initials: I
authors.lastname: Barna
authors.forename: Katalin
authors.initials: K
authors.lastname: Müllner
authors.forename: Anikó
authors.initials: A
authors.lastname: Reichart
authors.forename: Miklós
authors.initials: M
authors.lastname: Palkovits
mesh_terms: D000315:Adrenalectomy; D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000502:physiology; D001933:Brain Stem / Q000502:physiology*; D002946:Cisterna Magna; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood; D016308:Enkephalin, Leucine-2-Alanine / Q000008:administration & dosage / Q000494:pharmacology; D000431:Ethanol; D006179:Gyrus Cinguli / Q000502:physiology*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology; D008032:Limbic System / Q000502:physiology; D008297:Male; D008845:Microinjections; D051381:Rats; D017208:Rats, Wistar; D017465:Receptors, Opioid, delta / Q000819:agonists*; D012997:Solvents; D013276:Stomach Ulcer / Q000139:chemically induced / Q000503:physiopathology*; D001615:beta-Endorphin / Q000097:blood / Q000494:pharmacology
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D017465:Receptors, Opioid, delta; D012997:Solvents; D000431:Ethanol; D001615:beta-Endorphin; D016308:Enkephalin, Leucine-2-Alanine; D000324:Adrenocorticotropic Hormone; D003000:Clonidine; D003345:Corticosterone