Orexin-A promotes EEG changes but fails to induce anxiety in rats

Orexins (OXs) system has been suggested to play a key role in regulate processes related to arousal, including anxious behaviors. However, until now, the contribution of OXs in anxiogenic-like effects has not been completely clear, particularly in rats, whose results are not yet conclusive in behavioral-tests such as elevated-plus-maze test (EPM-test). The goal of this study was to explore the anxiogenic-like effect induced by orexin-A (OX-A) using two different paradigms; the EPM-test and simultaneously a quantitative index in vivo, the cortical-electroencephalographic-(EEG)-record. This index proposes that a low-frequency domain EEG, particularly 0.5-5-Hz (delta and low portion of theta-waves), is a key indicator to evaluate anxiety levels. We also explored whether the anxious effect of OX-A could be altered by an antagonist of dopamine-D2-receptor (D₂R) sulpiride (SUL). Our results showed that intracerebroventricular (i.c.v.) injection of a low dose of OX-A (140 pmol) did not increase anxiety levels in rats. On the other hand, cortical-EEG-activity showed only a decrease in delta-spectral-power but no changes in theta-potency. These data suggest that the reduction in delta-power induced by OX-A only keeps the animals awake and alert without changes in anxiety levels.