Social isolation and expression of serotonergic neurotransmission-related genes in several brain areas of male mice.

Early-life events influence brain development and evoke long-lasting behavioral consequences. Postweaning social isolation in rodents induces emotional and neurochemical alterations similar to those observed among some human psychopathologies. Central serotonergic neurotransmission is intimately involved in the observed adjustments, but the impact of social deprivation on serotonergic gene expression is unknown. We investigated the effects of prolonged early social isolation on emotion-related behaviors and 5-hydroxytryptamine (5-HT)-related gene transcription in mice. After weaning, male C57BL/6J mice were reared singly or in groups of four for 6 weeks. Gene expression of 5-HT(1A), 5-HT(1B), 5-HT(2A), 5-HT(2C), 5-HT(3A), 5-HT(6) and 5-HT(7) receptors and of 5-HT transporter and tryptophan hydroxylase-2 was determined by quantitative real-time polymerase chain reaction in distinct brain areas. Single-housed mice were hyperactive in a novel environment and showed signs of aggressive behavior. Housing condition did not alter weight gain or body temperature. Isolation markedly reduced transcription of all postsynaptic 5-HT receptors in the prefrontal cortex and reduced 5-HT(1B), 5-HT(2A) and 5-HT(2C) in both hypothalamus and midbrain. In contrast, the only alteration in the hippocampus was 5-HT(6) overexpression. Neither 5-HT transporter nor synthetic enzyme gene transcription differed between housing conditions. In conclusion, early social isolation in mice induces robust changes in postsynaptic 5-HT receptors gene transcription, motor hyperactivity and behavioral disinhibition. The overall pattern of decreased gene expression in the prefrontal cortex highlights its high vulnerability to environment. Furthermore, this is the first study to present a general representation of 5-HT-related gene expression in specific brain areas after social isolation and identifies novel candidates that may be critical for underlying molecular mechanisms.