Dynamic alterations of serotonergic metabolism and receptors during social isolation of low- and high-active mice.

Alterations induced by social isolation (1 day to 18 weeks) in low- and high-active mice (LAM and HAM) were studied in respect to serotonin metabolism, [3H]-8-OH-DPAT binding of presynaptic (midbrain), postsynaptic (hippocampus) 5-HT1A receptors and [3H]-ketanserin binding of cortical 5-HT2A receptors. Individual housing of mice was associated with reduction of serotonin metabolism, depending on isolation time and brain structure. Whereas a transient decrease in the striatum and cortex was detected between 1 week and 6 weeks, reduction of cerebellar and hippocampal serotonin metabolism was found later (12-18 weeks). Serotonergic systems of HAM were found to be more reactive to environmental disturbances, and their serotonin metabolism was more affected by social isolation. Isolation-induced upregulation of cortical 5-HT2A receptors was measured only in HAM. Densities of postsynaptic 5-HT1A receptors in the hippocampus did differ either in grouped or isolated mice. However, there were significant differences in hippocampal 5-HT1A receptor affinity, especially between 1 day and 3 weeks. Transient downregulation of presynaptic 5-HT1A receptors in the midbrain was found in isolated mice between 3 and 6 weeks. These results are discussed in terms of interactions between serotonergic alterations and isolation-induced aggression.