Autoradiographic analyses of 5-HT1A and 5-HT2A receptors after social isolation in mice.

Social isolation of rodents is used to model human psychopathological processes. In the present study, the effects of intermediate and long term isolation housing on postsynaptic 5-HT(1A) and 5-HT(2A) receptors were analyzed in male mice housed in groups or isolation for 4 and 12 weeks. [3H]8-OH-DPAT and [3H]ketanserin were used to label 5-HT(1A) and 5-HT(2A) receptors. Four representative sagittal sections (planes 1-4) were scored by in vitro autoradiography. Whereas after 4 weeks of housing both receptor densities were lowered significantly in isolated mice, after 12 weeks of housing only marginal isolation effects were seen. Intermediate isolation reduced 5-HT(1A) receptors especially in the lateral frontal, parietal and entorhinal cortex (-63%), in the lateral CA1-3 and dentate gyrus region of the hippocampus (-68%), in the basolateral, basomedial, central and medial amygdaloid nuclei (between -38 and -66%), and in the hypothalamus (-28%). 5-HT(2A) receptors were strongly reduced in the frontal cortex (between -47 and -74%), in the hippocampus (between -47 and -95%), in the striatum (between -66 and -76%), and in the accumbens nucleus (between -59 and -73%) in comparison to group housed control mice. After 12 weeks of isolation in the hippocampus continuously decreased 5-HT(1A) receptor densities were demonstrated (between -24 and -61%). But increased 5-HT(2A) receptor densities were seen in the lateral striatum (+86%) compared to control mice. Age-dependent effects were also found. After 12 weeks of group housing the 5-HT(1A) and 5-HT(2A) receptor densities were decreased (between -28 and -54%) in all analyzed brain regions in comparison to 4 weeks of group housing. Isolated animals showed diminished 5-HT(1A) receptor densities in the cortex (-14%) and hippocampus (-15%), but increased 5-HT(1A) receptor densities in the amygdala (+33%) after 12 weeks. The 5-HT(2A) receptor densities were increased in all analyzed regions (between +31 and +96%) after 12 weeks of isolation compared to 4 weeks. To explain these dynamic, time-dependent pattern of isolation-induced changes different regulation processes are supposed regarding 5-HT(1A) and 5-HT(2A) receptors. Besides metabolism-related adaptation processes also neurotransmitter and hormonal (e.g., glucocorticoid) interactions especially in limbic regions have to be considered.