title: Autoradiographic analyses of 5-HT1A and 5-HT2A receptors after social isolation in mice.
abstract: 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.
authors.affiliation: AG Neurobiologie, Klinik für Psychiatrie, TU, Dresden, Germany. lydia.schiller@mailbox.tu-dresden.de
authors.forename: Lydia
authors.initials: L
authors.lastname: Schiller
authors.forename: Monika
authors.initials: M
authors.lastname: Jähkel
authors.forename: Marion
authors.initials: M
authors.lastname: Kretzschmar
authors.forename: Peter
authors.initials: P
authors.lastname: Brust
authors.forename: Jochen
authors.initials: J
authors.lastname: Oehler
mesh_terms: D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D006799:Housing, Animal; D008297:Male; D051379:Mice; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000032:analysis* / Q000737:chemistry; D044263:Receptors, Serotonin, 5-HT1; D012934:Social Isolation; D013997:Time Factors
chemical_list: D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1