02 June 2011
GABAA receptor, glutamate decarboxylase, HAB, high anxiety-related behavior, amygdala, FosB, BLA, basolateral amygdala, CEA, central amygdala, EPM, elevated plus maze, GAD65, glutamic acid decarboxylase of 65 kilo Dalton, GAD67, glutamic acid decarboxylase of 67 kilo Dalton, HAB, high anxiety-related behavior, LAB, low anxiety-related behavior, MEA, medial amygdala, NAB, normal anxiety-related behavior, ROD, relative optical density
Anxiety disorders are the most prevalent central nervous system diseases imposing a high social burden to our society. Emotional processing is particularly controlled by GABA-ergic transmission in the amygdala. Using in situ hybridization and immunohistochemistry we now investigated changes in the expression of GABA synthesizing enzymes (GAD65 and GAD67), GABA A (α1–5, β1–3, γ1–2) and GABA B receptor subunits (GBBR1, GBBR2) in amygdaloid nuclei of high anxiety-related behavior (HAB) mice in comparison to mice selected for normal anxiety-related behavior (NAB). Levels of GAD65 and GAD67 mRNAs and protein, as well as those of GABA were increased in the amygdala of HAB mice. Relative to NAB controls, mRNA expression of the GABA A receptor subunits β1, β2 and γ2 was specifically increased in the basolateral amygdala of HAB mice while transcription of α5 and γ1 subunits was reduced in the central and medial amygdala. On the protein level, increases in β2 and γ2 subunit immunoreactivities were evident in the basolateral amygdala of HAB mice. No change in GABA B receptor expression was observed. These findings point towards an imbalanced GABA-ergic neurotransmission in the amygdala of HAB mice. On the other hand, FosB, a marker for neuronal activity, was increased in principal neurons of the basolateral amygdala in HAB mice, reflecting activation of excitatory neurons, possibly as a consequence of reduced GABA-ergic tonic inhibition through α5 and γ1 containing receptors. Ultimately these mechanisms may lead to the compensatory activation of GABA transmission, as indicated by the increased expression of GAD65/67 in HAB mice.