Involvement of orexin-A in the regulation of neuronal activity and emotional behaviors in central amygdala in rats

The amygdala is a complex structure involved in the regulation of emotional behaviors including fear and anxiety. The central amygdala is the main output of the amygdala and plays an important role in emotional processing. Recent studies indicate that orexin, a kind of neuropeptides responsible for maintaining wakefulness, is also associated with emotion-related behaviors, such as depression- and anxiety-like behaviors. Central amygdala receives orexinergic fibers originating from the lateral hypothalamus and expresses OX1 receptors in rats. To test the electrophysiological and behavioral effects of orexins in the central amygdala, single unit in vivo extracellular recordings, open field and elevated plus maze tests were performed in rats. Micro-pressure administration of orexin-A (0.01 mmol/L) increased the firing rate in 18 out of the 31 central amygdala neurons, while the other 13 neurons were not excited by orexin-A. The excitatory effects of orexin-A on central amygdala neurons were mainly mediated by OX1 receptors rather than OX2 receptors. Orexin-B (0.01 mmol/L) did not change the firing activity in all recorded central amygdala neurons. Selectively blocking OX1 receptors by SB334867 (0.01 mmol/L) significantly decreased the spontaneous firing rate in 14 out of the 33 central amygdala neurons, leaving the remaining 19 neurons were not affected. However, blocking OX2 receptors by TCS-OX2-29 (0.01 mmol/L) did not change the firing activity. Finally, both open field test and elevated plus maze test showed that bilateral microinjection of orexin-A into the central amygdala induced significantly anxiolytic-like behaviors. The specific OX1 receptor antagonist tended to produce opposite effects although there was no statistical difference. The present electrophysiological and behavioral studies suggested that orexin-A participates in anxiety-like behaviors by modulating the spontaneous firing activity of central amygdala neurons.