Department of Anesthesiology

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The anxiety-like phenotype of 5-HT receptor null mice is associated with genetic background-specific perturbations in the prefrontal cortex GABA-glutamate system.

TitleThe anxiety-like phenotype of 5-HT receptor null mice is associated with genetic background-specific perturbations in the prefrontal cortex GABA-glutamate system.
Publication TypeJournal Article
Year of Publication2006
AuthorsBruening S, Oh E, Hetzenauer A, Escobar-Alvarez S, Westphalen RI, Hemmings HC, Singewald N, Shippenberg T, Toth M
JournalJ Neurochem
Volume99
Issue3
Pagination892-9
Date Published2006 Nov
ISSN0022-3042
KeywordsAnimals, Anxiety, Behavior, Animal, Blotting, Western, Chromatography, High Pressure Liquid, Excitatory Amino Acid Transporter 3, gamma-Aminobutyric Acid, Genes, fos, Glutamic Acid, Immunohistochemistry, Mice, Mice, Inbred C57BL, Mice, Knockout, Microdialysis, Phenotype, Potassium Chloride, Prefrontal Cortex, Receptor, Serotonin, 5-HT1A, Sodium, Stress, Psychological, Synaptosomes
Abstract

A deficit in the serotonin 5-HT(1A) receptor has been found in panic and post-traumatic stress disorders, and genetic inactivation of the receptor results in an anxiety-like phenotype in mice on both the C57Bl6 and Swiss-Webster genetic backgrounds. Anxiety is associated with increased neuronal activity in the prefrontal cortex and here we describe changes in glutamate and GABA uptake of C57Bl6 receptor null mice. Although these alterations were not present in Swiss-Webster null mice, we have previously reported reductions in GABA(A) receptor expression in these but not in C57Bl6 null mice. This demonstrates that inactivation of the 5-HT(1A) receptor elicits different and genetic background-dependent perturbations in the prefrontal cortex GABA/glutamate system. These perturbations can result in a change in the balance between excitation and inhibition, and indeed both C57Bl6 and Swiss-Webster null mice show signs of increased neuronal excitability. Because neuronal activity in the prefrontal cortex controls the extent of response to anxiogenic stimuli, the genetic background-specific perturbations in glutamate and GABA neurotransmission in C57Bl6 and Swiss-Webster 5-HT(1A) receptor null mice may contribute to their shared anxiety phenotype. Our study shows that multiple strains of genetically altered mice could help us to understand the common and individual features of anxiety.

DOI10.1111/j.1471-4159.2006.04129.x
Alternate JournalJ. Neurochem.
PubMed ID16925594
Grant ListMH-58669 / MH / NIMH NIH HHS / United States