Antibodies and antisense oligonucleotide for probing the distribution and putative functions of central 5-HT6 receptors

Among the recently cloned serotonin (5-hydroxytryptamine, 5-HT) receptors, the 5-HT6 subtype is of special interest for at least two reasons: 1) if is abundant in limbic areas which participate in the control of mood and emot ion; and 2) some antidepressants and antipsychotics ave potent 5-HT6 recept or antagonists. Studies using polyclonal anti-5-HT6 receptor antibodies and an antisense oligonucleotide were performed in order to investigate furthe r the function(s) of 5-HT6 receptors in the rat brain. Immunocytochemistry at the light and electron microscope levels showed that 5-HT6 receptors are mainly confined to the dendritic compartment, suggesting that they could m ediate 5-HT actions an neuronal firing. lit some limbic areas, 5-HT6 recept or-like immunoreactivity is also associated with neuronal cilia with yet un known functions. Continuous i.c.v. infusion with an antisense oligonucleoti de for 3-4 days resulted in decreased 5-HT6 receptor-like immunostaining of the nucleus accumbens and anxiogenic behaviours in the social interaction and elevated plus maze tests. Selective 5-HT6 receptor ligands are eagerly expected to investigate further the potential implication of these receptor s in limbic-dependent behaviours. (C) 1999 American College of Neuropsychop harmacology. Published by Elsevier Science Inc.