Treatment of Clonidine Based Attentional Deficits by Intranasal Orexin A Administration

Clonidine, an alpha-2 receptor agonist of the adrenergic system, has not been thoroughly examined regarding its attentional impact on healthy rats. The limited number of studies, however, have shown that clonidine impairs attentional ability (Bushnell et al., 1997). Furthermore, no significant steps have been taken to investigate the orexinergic system’s ability to attenuate attentional deficits caused by clonidine’s noradrenergic disruption although there is evidence to demonstrate orexinergic neurons can provide excitation to inhibited noradrenergic neurons (Hagan et al., 1999). This leads to the question: are the attentional deficits caused by the disruption of noradrenergic neurons with intraperitoneal administered clonidine reversible with the utility of intranasal orexin A? Sprague-Dawley rats (n = 11) were trained in a visual sustained attention task and received vehicle-only, clonidine-only, or orexin A and clonidine. The experimental results demonstrated that clonidine did create significant attentional impairments, as shown with decreased performance at the 500 ms signal duration and increased number of omissions. However, there were no significant decreases to non-signal trial accuracy. In terms of orexin A’s therapeutic potential, there was no significant ability to reverse the attentional deficits. The attentional impairments created by clonidine were transient, as there was no significant difference in attentional performance between drug administration and non-drug administration days. In conclusion, clonidine was able to create transient attentional deficits, and orexin A was unable to treat these attentional deficits.