Anxiety and increased 5-HT1A receptor response in NCAM null mutant mice.
Mice deficient in the neural cell adhesion molecule (NCAM) show behavioral abnormalities as adults, including altered exploratory behavior, deficits in spatial learning, and increased intermale aggression. Here, we report increased anxiety-like behavior of homozygous (NCAM-/-) and heterozygous (NCAM/-) mutant mice in a light/dark avoidance test, independent of genetic background and gender. Anxiety-like behavior was reduced in both NCAM+/+ and NCAM-/- mice by systemic administration of the benzodiazepine agonist diazepam and the 5-HT1A receptor agonists buspirone and 8-OH-DPAT. However, NCAM-/- mice showed anxiolytic-like effects at lower doses of buspirone and 8-OH-DPAT than NCAM+/+ mice. Such increased response to 5-HT1A receptor stimulation suggests a functional change in the serotonergic system of NCAM-/- mice, likely involved in the control of anxiety and aggression. However, 5-HT1A receptor binding and tissue content of serotonin and its metabolite 5-hydroxyindolacetic acid were found unaltered in every brain area of NCAM-/- mice investigated, indicating that expression of 5-HT1A receptors as well as synthesis and release of serotonin are largely unchanged in NCAM-/- mice. We hypothesize a critical involvement of endogenous NCAM in serotonergic transmission via 5-HT1A receptors and inwardly rectifying K+ channels as the respective effector systems.
Stork
O
O
Department of Neurobiology, Swiss Federal Institute of Technology, Hönggerberg, CH 8093 Zürich, Switzerland.
Welzl
H
H
Wotjak
C T
CT
Hoyer
D
D
Delling
M
M
Cremer
H
H
Schachner
M
M
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology / Q000627:therapeutic use; D001007:Anxiety / Q000188:drug therapy* / Q000523:psychology*; D001345:Autoradiography; D001667:Binding, Competitive; D001923:Brain Chemistry / Q000502:physiology; D002065:Buspirone; D003975:Diazepam / Q000494:pharmacology / Q000627:therapeutic use; D005106:Exploratory Behavior / Q000187:drug effects; D005838:Genotype; D006897:Hydroxyindoleacetic Acid / Q000032:analysis; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D019006:Neural Cell Adhesion Molecules / Q000187:drug effects*; D015221:Potassium Channels / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000032:analysis; D017366:Serotonin Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use; D013037:Spatial Behavior / Q000187:drug effects
D014151:Anti-Anxiety Agents; D019006:Neural Cell Adhesion Molecules; D015221:Potassium Channels; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D003975:Diazepam; D002065:Buspirone