Systemic and intrabasalis administration of the orexin-1 receptor antagonist, SB-334867, disrupts attentional performance in rats

Orexin neurons project to a number of brain regions, including onto basal forebrain cholinergic neurons. Basal forebrain corticopetal cholinergic neurons are known to be necessary for normal attentional performance. Thus, the orexin system may contribute to attentional processing. We tested whether blockade of orexin-1 receptors would disrupt attentional performance. Rats were trained in a two-lever sustained attention task that required discrimination of a visual signal (500, 100, 25 ms) from trials with no signal presentation. Rats received systemic or intrabasalis administration of the orexin-1 receptor antagonist, SB-334867, prior to task performance. Systemic administration of the orexin-1 receptor antagonist, SB-334867 (5.0 mg/kg), decreased detection of the longest duration signal. Intrabasalis SB-334867 (0.60 mu g) decreased overall accuracy on trials with longer signal durations. These findings suggest that orexins contribute to attentional processing, although neural circuits outside of basal forebrain corticopetal cholinergic neurons may mediate some of these effects.