Involvement of central histaminergic and cholinergic systems in the morphine-induced increase in blood-brain barrier permeability to sodium fluorescein in mice.
Morphine (5 mg/kg, s.c.) caused a submaximal increase in the brain level of sodium fluorescein administered i.v. Histamine H1-antagonists, diphenhydramine and mepyramine, given either i.p. or i.c.v., had no significant influence on the effect of morphine. H2-Antagonists, cimetidine and ranitidine, administered i.c.v., but not i.p., significantly inhibited the morphine effect. alpha-Fluoromethylhistidine, a specific histidine decarboxylase inhibitor (given i.p. and i.c.v.) and antimuscarinic drugs, atropine and biperiden, but not methylatropine (given i.p.) also significantly reduced the morphine effect. Physostigimine (i.p.) significantly enhanced the effects of 0.5 and 1 mg/kg of morphine. Similar effects of histaminergic and cholinergic drugs were also observed on the buprenorphine- and DAGO-induced increase in blood-brain barrier (BBB) permeability to sodium fluorescein. None of the treatments with 6-hydroxydopamine, alpha-methyltyrosine, 5,7-dihydroxytryptamine or p-chlorophenylamine had any significant effect on the morphine-induced increase in BBB permeability. These findings suggest that the activation of brain H2-receptors by neuronal histamine and muscarinic receptors by acetylcholine is involved in the increase in BBB permeability to sodium fluorescein caused by mu opioid receptor agonists.
Oishi
R
R
Department of Pharmacology, Okayama University Medical School, Japan.
Baba
M
M
Nishibori
M
M
Itoh
Y
Y
Saeki
K
K
D000109:Acetylcholine / Q000378:metabolism / Q000502:physiology; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects; D002395:Catecholamines / Q000378:metabolism / Q000502:physiology; D005452:Fluoresceins; D006632:Histamine / Q000378:metabolism / Q000502:physiology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009020:Morphine / Q000494:pharmacology*; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D010276:Parasympatholytics / Q000494:pharmacology; D011957:Receptors, Opioid / Q000502:physiology; D017450:Receptors, Opioid, mu; D012701:Serotonin / Q000378:metabolism / Q000502:physiology
D002395:Catecholamines; D005452:Fluoresceins; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D010276:Parasympatholytics; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D012701:Serotonin; D009020:Morphine; D006632:Histamine; D000109:Acetylcholine