Schiller Lydia, Jähkel Monika, Kretzschmar Marion, Brust Peter, Oehler Jochen
AG Neurobiologie, Klinik für Psychiatrie, TU, Dresden, Germany.
Brain Res. 2003 Aug 8;980(2):169-78. doi: 10.1016/s0006-8993(03)02832-4.
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.
