Chronic activation of the 5-HT(2) receptor reduces 5-HT neurite density as studied in organotypic slice cultures.
The serotonin system densely innervates the brain and is implicated in psychopathological processes. Here we studied the effect of serotonin and serotonin pharmacological compounds on the outgrowth of serotonergic projections using organotypic slice co-cultures of hippocampus and dorsal raphe nuclei. Immunocytochemical analysis showed that several serotonergic neurites had grown into the target slice within 7 days in culture, after which the neurite density stabilized. These projections expressed the serotonin-synthesizing enzyme Tryptophan hydroxylase and the serotonin transporter and contained several serotonin-positive varicosities that also accumulated presynaptic markers. Chronic application of a 5-HT(2) agonist reduced the serotonergic neurite density, without effects on survival of serotonergic neurons. In contrast, application of a 5-HT(1A) agonist or the serotonin transporter inhibitor fluoxetine did not affect serotonergic neurite density. We conclude that serotonergic connectivity was reproduced in vitro and that the serotonin neurite density is inhibited by chronic activation of the 5-HT(2) receptor.
Dudok
Jacobus J
JJ
Department of Functional Genomics, Center for Neurogenomics and Cognitive Research (CNCR), Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Groffen
Alexander J A
AJ
Witter
Menno P
MP
Voorn
Pieter
P
Verhage
Matthijs
M
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D018920:Coculture Techniques; D004334:Drug Administration Schedule; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D006624:Hippocampus / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D009434:Neural Pathways / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D016501:Neurites / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D009924:Organ Culture Techniques; D011903:Raphe Nuclei / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D044348:Receptors, Serotonin, 5-HT2 / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D058826:Serotonin 5-HT2 Receptor Agonists; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014365:Tryptophan Hydroxylase / Q000378:metabolism
D044348:Receptors, Serotonin, 5-HT2; D058826:Serotonin 5-HT2 Receptor Agonists; D050486:Serotonin Plasma Membrane Transport Proteins; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D014365:Tryptophan Hydroxylase