title: Ammonium acetate challenge in experimental chronic hepatic encephalopathy induces a transient increase of brain 5-HT release in vivo.
abstract: Ammonia has been shown to cause release of neurotransmitters such as serotonin (5-hydroxytryptamine; 5-HT) from synaptosomal preparations in vitro. In the present study, frontal neocortical extracellular levels of 5-HT and its major metabolite, 5-hydroxyindole-3-acetic acid (5-HIAA), were determined in vivo by the use of microdialysis in portacaval shunted (PCS) rats, an experimental model of chronic hepatic encephalopathy (HE), prior to and after an acute coma-inducing administration of ammonium acetate (NH4Ac; 5.2 mmol/kg, i.p.). PCS rats displayed elevated (P < 0.01) 5-HIAA but unaltered 5-HT extracellular levels compared with controls, supporting the contention of an increased neocortical 5-HT metabolism but unaltered neuronal 5-HT output in chronic HE. However, a transient elevation of extracellular 5-HT levels was observed when PCS-NH4Ac rats were in coma. Increased brain ammonia may thus augment neuronal 5-HT release in chronic HE, which in turn could be a causative for precipitation of more severe stages of HE.
authors.affiliation: Department of Clinical Pharmacology, Lund University Hospital, Sweden.
authors.forename: P B
authors.initials: PB
authors.lastname: Bergqvist
authors.forename: S
authors.initials: S
authors.lastname: Hjorth
authors.forename: R M
authors.initials: RM
authors.lastname: Audet
authors.forename: G
authors.initials: G
authors.lastname: Apelqvist
authors.forename: F
authors.initials: F
authors.lastname: Bengtsson
authors.forename: R F
authors.initials: RF
authors.lastname: Butterworth
mesh_terms: D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D006501:Hepatic Encephalopathy / Q000139:chemically induced*; D008297:Male; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*
chemical_list: D000085:Acetates; D012701:Serotonin; C018824:ammonium acetate