Article thumbnail
Location of Repository

In socially isolated mice, the reversal of brain allopregnanolone down-regulation mediates the anti-aggressive action of fluoxetine

By Graziano Pinna, Erbo Dong, Kinzo Matsumoto, Erminio Costa and Alessandro Guidotti

Abstract

Social isolation (SI) of male mice lasting >4 weeks is associated with aggression toward intruders and a down-regulation of brain allopregnanolone (Allo) content. SI of female mice fails to down-regulate brain Allo content or to induce aggressiveness. Fluoxetine (Prozac in clinical use) is an S- and R-fluoxetine (FLX) mixture, which in mammals is metabolized into S- and R-norfluoxetine (NFLX). The S isomers of FLX and NFLX are more active than their respective R isomers in normalizing brain Allo down-regulation and in reducing the aggressiveness induced by SI. Thus, FLX stereospecifically reduces brain Allo down-regulation and the aggressiveness induced by SI, whereas serotonin (5-HT) uptake inhibition lacks stereospecificity. The doses of S-FLX and S-NFLX that reduce aggressiveness and Allo brain content down-regulation induced by SI are at least one order of magnitude lower than the doses that block 5-HT reuptake. Doses of imipramine that inhibit 5-HT uptake neither reduce aggressiveness nor normalize brain Allo down-regulation. We conclude that Allo brain content normalization is a better candidate than 5-HT reuptake inhibition to explain the reduction of aggressiveness elicited by S-FLX and S-NFLX

Topics: Biological Sciences
Publisher: The National Academy of Sciences
Year: 2003
DOI identifier: 10.1073/pnas.0337642100
OAI identifier: oai:pubmedcentral.nih.gov:149954
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://dx.doi.org/10.1073/pnas... (external link)
  • Suggested articles


    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.