Brain neurosteroids in gender-related aggression induced by social isolation.
Genetic, environmental, or hormonal factors and their interactions have been implicated in the expression of gender-related aggressive behavior in humans. Several independent lines of evidence support the role of hormonal and environmental factors in the aggressive behavior of experimental animals. Social isolation (SI) for 2-4 weeks in male but not in female mice results in the expression of aggression to a same-sex intruder. Long-term treatment (3 weeks) with anabolic steroids during SI in female mice induces aggressive behavior toward a male intruder of a severity similar to that observed in socially isolated (SI) male mice. The induced aggression in male and female mice is associated with a decrease of brain allopreg-nanolone (Allo). In SI male mice, aggression can be prevented by treatment with L-methionine (MET), which has also been shown to decrease reelin and GAD67 mRNA expression and maintain normal brain Allo content. The histone deacetylase inhibitor valproic acid can reverse this process, suggesting that histone tail acetylation may reverse the action of MET. We conclude that during social isolation, aggression can be controlled either by preventing Allo downregulation (e.g., by treatment with MET) or by direct administration of Allo or of agents (e.g., fluoxetine) that upregulate brain Allo content in SI mice.
Pinna
Graziano
G
Psychiatric Institute, Department of Psychiatry, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612, USA. gpinna@psych.uic.edu
Agis-Balboa
Roberto C
RC
Doueiri
Mohemed-Salim
MS
Guidotti
Alessandro
A
Costa
Erminio
E
D000374:Aggression / Q000523:psychology*; D000818:Animals; D005260:Female; D018682:GABA Agents / Q000494:pharmacology; D012739:Gonadal Steroid Hormones / Q000494:pharmacology; D008297:Male; D008715:Methionine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051379:Mice; D018377:Neurotransmitter Agents / Q000378:metabolism / Q000502:physiology*; D011280:Pregnanolone / Q000494:pharmacology; D000091042:Reelin Protein; D012727:Sex Characteristics; D012934:Social Isolation / Q000523:psychology*; D013256:Steroids / Q000378:metabolism / Q000502:physiology*; D014635:Valproic Acid / Q000494:pharmacology
D018682:GABA Agents; D012739:Gonadal Steroid Hormones; D018377:Neurotransmitter Agents; D000091042:Reelin Protein; D013256:Steroids; D014635:Valproic Acid; D008715:Methionine; D011280:Pregnanolone; C000717127:RELN protein, human; C000717128:Reln protein, mouse