Amygdalic levels of monoamines, amino acids and nitric oxide rise upon exposure to conditioned fear stress without elevation of amino acids

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Conditioned fear is an artificial stress, induced by a stimulus, such as a tone, that does not elicit fear in nature. The amygdala is considered to be the area involved in acquisition, consolidation and recall of fear. The present study was designed to continuously monitor changes in extracellular levels of glutamate, NO_3^-, dopamine and serotonin in the amygdala, at the acquisition of conditioned fear on Day 1 and at fear recall in response to a tone as a conditioned stimulus on Day 2, using the in vivo microdialysis method. Glutamate was elevated only on Day 1, while dopamine, serotonin and NO_3^- rose on both days. Using a in-vivo brain microdialysis method, in addition, we investigated effects of intraperitoneal administration with lithium, imipramine, and diazepam on NO_3^- levels in the rat amygdala. Lithium significantly declined, but that of imipramine raised NO_3^- levels as compared with control. These suggest that lithium and imipramine induce contrastive effects on nitric oxide related systems in the brain. We also investigated the influence of peripherally administered interferon-alpha on amino acid levels in the brain. One day of interferon-alpha treatment induced no significant changes in any of these amino acids. After 4 days of interferon-alpha injections, glutamate, glycine, taurine and gamma-aminobutyric acid levels were significantly higher than those in the control frontal cortex, striatum, hippocampus, amygdala, and thalamus. However, most of these amino acids returned to approximately basal levels, or even lower, with 14-day-treatment.