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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2001-12-17
pubmed:abstractText
The steroid sulfatase enzyme (STS) regulates the formation of dehydroepiandrosterone (DHEA) from dehydroepiandrosterone-sulfate (DHEAS). DHEAS is a well-known negative allosteric modulator of the GABA(A) receptor-gated chloride channels. It is classified as an excitatory neurosteroid. The implication of GABA(A) receptor activity in aggressive behavior in rodents is well-documented. In addition a genetic correlation between STS level in the liver and aggressive behavior across 12 strains of mice suggest that STS activity could be involved in aggression in mice. We assessed herein whether COUMATE (an STS inhibitor) and DHEAS modulate aggression in CBA/H mice. We hypothesized that inhibiting STS activity in vivo followed by DHEAS injections which increase the level of sulfated steroid that cross the blood-brain barrier and then modulate neurotransmitter receptors could modify the attack behavior in mice. COUMATE (10 mg/kg) was administrated p.o. alone or in combination with the neurosteroid DHEAS (0-50 mg/kg) i.p. Animals were thereafter tested for aggression. A single dose of COUMATE significantly inhibited STS activity both in the brain (70.57%) and in the liver (87%) 24 h following administration. Behavioral tests showed that the inhibitor and DHEAS enhanced aggressive behavior when animals were simultaneously subjected to both molecules. These results confirm the correlation between aggressive behavior and STS concentration in mice. In addition, we confirm that the steroid metabolism can modulate the behavior in rodents.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0006-8993
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
922
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
216-22
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed-meshheading:11743952-Aggression, pubmed-meshheading:11743952-Animals, pubmed-meshheading:11743952-Arylsulfatases, pubmed-meshheading:11743952-Behavior, Animal, pubmed-meshheading:11743952-Brain, pubmed-meshheading:11743952-Coumarins, pubmed-meshheading:11743952-Dehydroepiandrosterone Sulfate, pubmed-meshheading:11743952-Dose-Response Relationship, Drug, pubmed-meshheading:11743952-Enzyme Inhibitors, pubmed-meshheading:11743952-Female, pubmed-meshheading:11743952-Liver, pubmed-meshheading:11743952-Male, pubmed-meshheading:11743952-Methylcellulose, pubmed-meshheading:11743952-Mice, pubmed-meshheading:11743952-Mice, Inbred CBA, pubmed-meshheading:11743952-Receptors, GABA-A, pubmed-meshheading:11743952-Steryl-Sulfatase, pubmed-meshheading:11743952-Sulfonamides, pubmed-meshheading:11743952-Synaptic Transmission, pubmed-meshheading:11743952-gamma-Aminobutyric Acid
pubmed:year
2001
pubmed:articleTitle
Aggressive behavior induced by the steroid sulfatase inhibitor COUMATE and by DHEAS in CBA/H mice.
pubmed:affiliation
FRE 2134 C.N.R.S. Génétique, Neurogénétique, Comportement, Institut de Transgénose, 3B rue de la Férollerie, 45071 Orléans La Source, France.
pubmed:publicationType
Journal Article