ABSTRACT
The role of genetic and environmental factors as well as brain neurochemistry in regulating aggressive and submissive behaviors in animals are considered. We present a review of data on changes in brain monoaminergic activity (synthesis, catabolism, receptors) and on the expression of monoaminergetic genes under repeated daily agonistic confrontations in male mice. A repeated experience of aggression was shown to result in the total activation of the dopaminergic system and the inhibition of the serotonergic one. This was accompanied by a decrease in the mRNA level of the catechol-O-methyltransferase gene in the midbrain and an increase of the mRNA level of the dopamine transporter and tyrosine hydroxylase genes in the ventral tegmental area of aggressive male mice. Repeated experience of social defeats produced dynamic changes in the serotonergic system of some brain areas and an increase of the mRNA level of the serotonin transporter and monoamine oxidase A genes in the midbrain raphe nuclei. Theoretical and methodological possibilities of the proposed ethological approach for studying molecular mechanisms of agonistic behavior are discussed in the context of the fundamental problem of investigating the ways of regulation from behavior to gene.
Subject(s)
Biogenic Monoamines/metabolism , Gene Expression Regulation , Genetics, Behavioral , Animals , Catechol O-Methyltransferase/genetics , Male , Membrane Glycoproteins/genetics , Membrane Transport Proteins/genetics , Mice , Monoamine Oxidase/genetics , Nerve Tissue Proteins/genetics , RNA, Messenger/genetics , Serotonin Plasma Membrane Transport ProteinsABSTRACT
Serotonin transporter and monoamine oxidase (MAO) A are involved in the inactivation of serotonin. The former is responsible for serotonin re-uptake from the synapse, whereas the latter catalyzes serotonin deamination in presynaptic terminals. Expression of serotonin transporter and MAO A genes was investigated in raphe nuclei of midbrain of CBA/Lac male mice with repeated experience of social victories or defeats in 10 daily aggressive confrontations. The amount of cDNA of these genes was evaluated using multiplex RT-PCR. Two independent experiments revealed that the defeated mice were characterized by significantly higher levels of serotonin transporter and MAO A mRNAs than the control and aggressive animals. Increased expression of MAO A and serotonin transporter genes is suggested to reflect the accelerated serotonin degradation in response to activation of the serotonergic system functioning induced by social stress. Significant positive correlation between MAO A and serotonin transporter mRNA levels suggests common pathways of regulation of transcriptional activity of these genes.
Subject(s)
Carrier Proteins/biosynthesis , Dominance-Subordination , Membrane Glycoproteins/biosynthesis , Membrane Transport Proteins , Monoamine Oxidase/biosynthesis , Nerve Tissue Proteins , Raphe Nuclei/metabolism , Serotonin/metabolism , Aggression , Animals , Carrier Proteins/genetics , Humans , Male , Membrane Glycoproteins/genetics , Mice , Mice, Inbred CBA , Monoamine Oxidase/genetics , Polymerase Chain Reaction , RNA, Messenger/analysis , Serotonin Plasma Membrane Transport ProteinsABSTRACT
Tyrosine hydroxylase (TH) and dopamine transporter (DAT) mRNA levels in the ventral tegmental area (VTA) of midbrain were measured by multiplex RT-PCR in male mice with repeated experience of social victories (winners) and social defeats (losers) in 10 daily agonistic confrontations. Two independent experiments revealed enhanced TH and DAT mRNA levels in VTA of the winners in comparison with the losers and controls (animals after 5 days of individual housing). A positive correlation between DAT and TH mRNA levels was shown.
