Autoradiographic analyses of 5-HT_1A and 5-HT_2A 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.