title: Cerebrospinal fluid monoamine and metabolite concentrations and aggression in rats.
abstract: In humans and other primates low cerebrospinal fluid (CSF) levels of the major serotonin (5-HT) metabolite 5-hydroxyindoleacetic acid (5-HIAA) have been correlated to high aggressiveness. This finding forms the basis of the 5-HT deficiency hypothesis of aggression. Surprisingly, this correlation has not been confirmed in rodents so far, while manipulation studies aimed to investigate the link between 5-HT and aggressive behaviour are mostly carried out in rodents. In this study the relation between aggression and CSF monoamine and metabolite concentrations was investigated in male Wildtype Groningen rats. In sharp contrast to the hypothesis and our expectation, a clear positive correlation was found between the individual level of trait-like aggressiveness and CSF concentrations of 5-HT, 5-HIAA, norepinephrine (NE), dopamine (DA), and 3,4-dihydroxyphenylacetic acid (DOPAC). Shortly after the acute display of aggressive behaviour (as a state-like phenomenon), decreased 5-HT levels and an increase in 5-HIAA/5-HT ratio and NE concentrations were found. Surprisingly, pharmacological challenges known to influence 5-HT transmission and aggressive behaviour did not affect CSF 5-HT and 5-HIAA concentrations, only the NE level was increased. Lesioning 5-HT terminals by 5,7-dihydroxytryptamine (5,7-DHT) administration caused a decrease in CSF 5-HT and 5-HIAA, but without affecting aggressive behaviour. The observed positive correlation between CSF 5-HIAA and trait aggressiveness makes it questionable whether a direct extrapolation of neurobiological mechanisms of aggression between species is justified. Interpretation of CSF metabolite levels in terms of activity of neural substrates requires a far more detailed knowledge of the dynamics and kinetics of a neurotransmitter after its release.
authors: Department of Animal Physiology, Biology, University of Groningen, Haren, The Netherlands. B.J.van.der.Vegt@biol.rug.nl
authors: Bea J
authors: BJ
authors: van der Vegt
authors: Natasja
authors: N
authors: Lieuwes
authors: Thomas I F H
authors: TI
authors: Cremers
authors: Sietse F
authors: SF
authors: de Boer
authors: Jaap M
authors: JM
authors: Koolhaas
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000134:cerebrospinal fluid; D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000374:Aggression / Q000502:physiology*; D000818:Animals; D015306:Biogenic Monoamines / Q000134:cerebrospinal fluid*; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000134:cerebrospinal fluid; D005277:Fenfluramine / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D008297:Male; D009638:Norepinephrine / Q000134:cerebrospinal fluid; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000134:cerebrospinal fluid; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
chemical_list: D015102:3,4-Dihydroxyphenylacetic Acid; D015116:5,7-Dihydroxytryptamine; D015306:Biogenic Monoamines; D004298:Dopamine; D005277:Fenfluramine; D006897:Hydroxyindoleacetic Acid; D009638:Norepinephrine; D010879:Piperazines; D011725:Pyridines; D012701:Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; C079549:4-(benzodioxan-5-yl)-1-(indan-2-yl)piperazine; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide