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) it is abundant in limbic areas which participate in the control of mood and emotion; and 2) some antidepressants and antipsychotics are potent 5-HT6 receptor antagonists. Studies using polyclonal anti-5-HT6 receptor antibodies and an antisense oligonucleotide were performed in order to investigate further 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 mediate 5-HT actions on neuronal firing. In some limbic areas, 5-HT6 receptor-like immunoreactivity is also associated with neuronal cilia with yet unknown functions. Continuous i.c.v. infusion with an antisense oligonucleotide 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 receptors in limbic-dependent behaviours.
Hamon
M
M
INSERM Neuropsychopharmacology Unit 288, Faculty of Medicine Pitié-Salpêtrière, Paris, France.
Doucet
E
E
Lefèvre
K
K
Miquel
M C
MC
Lanfumey
L
L
Insausti
R
R
Frechilla
D
D
Del Rio
J
J
Vergé
D
D
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D000918:Antibody Specificity; D001369:Axons / Q000502:physiology / Q000648:ultrastructure; D001921:Brain / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D003712:Dendrites / Q000502:physiology / Q000648:ultrastructure; D007150:Immunohistochemistry; D008297:Male; D016253:Microscopy, Immunoelectron; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000502:physiology / Q000648:ultrastructure; D020319:Oligodeoxyribonucleotides, Antisense; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D017729:Presynaptic Terminals / Q000502:physiology / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000032:analysis / Q000737:chemistry / Q000502:physiology*
D000906:Antibodies; D020319:Oligodeoxyribonucleotides, Antisense; D010446:Peptide Fragments; D011985:Receptors, Serotonin; C097216:serotonin 6 receptor