title: Ammonia causes decreased brain monoamines in fathead minnows (Pimephales promelas).
abstract: Hyperammonemia, arising from variety of disorders, leads to severe neurological dysfunction. The mechanisms of ammonia toxicity in brain are not completely understood. This study investigated the effects of ammonia on monoaminergic systems in brains of fathead minnows (Pimephales promelas). Fish serve as a good model system to investigate hyperammonemic effects on brain function since no liver manipulations are necessary to increase endogenous ammonia concentrations. Using high performance liquid chromatography with electrochemical detection, monoamines and some associated metabolites were measured from whole brain homogenate. Adult males were exposed for 48 h to six different concentrations of ammonia (0.01-2.36 mg/l unionized) which bracketed the 96-h LC(50) for this species. Ammonia concentration-dependent decreases were found for the catecholamines (norepinephrine and dopamine) and the indoleamine serotonin (5-HT). After an initial increase in the 5-HT precursor 5-hydroxytryptophan it too decreased with increasing ammonia concentrations. There were also significant increases in the 5-HIAA/5-HT and DOPAC/DA ratios, often used as measures of turnover. There were no changes in epinephrine (Epi) or monoamine catabolites (DOPAC, 5-HIAA) at any ammonia concentrations tested. Results suggest that ammonia causes decreased synthesis while also causing increased release and degradation. Increased release may underlie behavioral reactions to ammonia exposure in fish. This study adds weight to a growing body of evidence demonstrating that ammonia leads to dysfunctional monoaminergic systems in brain which may underlie neurological symptoms associated with human disorders such as hepatic encephalopathy.
authors.affiliation: Avera Research Institute, Sioux Falls, SD 57105, USA.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Ronan
authors.forename: Mark P
authors.initials: MP
authors.lastname: Gaikowski
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Hamilton
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Buhl
authors.forename: Cliff H
authors.initials: CH
authors.lastname: Summers
mesh_terms: D000641:Ammonia / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003530:Cyprinidae / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007928:Lethal Dose 50; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D018709:Statistics, Nonparametric; D014873:Water Pollutants / Q000633:toxicity*
chemical_list: D015306:Biogenic Monoamines; D014873:Water Pollutants; D012701:Serotonin; D000641:Ammonia; D004298:Dopamine; D009638:Norepinephrine