The Role of the Neurokinin-1 Receptor in Stress-Induced Reinstatement of Alcohol and Cocaine Seeking

Abstract

Neurokinin-1 receptors (NK1Rs) have been shown to mediate alcohol and opiate, but not cocaine reward in rodents. We recently reported that NK1R antagonism also blocks stress-induced reinstatement of alcohol seeking in rats, but it is presently unknown whether these antirelapse properties extend to other drug classes. Although some work has suggested that intracranial substance P (SP) infusion reinstates cocaine seeking following extinction, no studies have indicated a direct role for the NK1R in reinstatement of cocaine seeking. Here, we explored the effect of the NK1R antagonist L822429 on yohimbine-induced reinstatement of alcohol or cocaine seeking in Long-Evans rats. Consistent with our previous findings with footshock-induced reinstatement of alcohol seeking in Wistar rats, we found that L822429 attenuates yohimbine-induced reinstatement of alcohol seeking, but does not affect baseline alcohol self-administration. We observed a similar suppression of yohimbine-induced reinstatement of cocaine seeking by L822429, and found that Long-Evans rats exhibit greater sensitivity to NK1R antagonism than Wistar rats. Accordingly, Long-Evans rats exhibit differences in the expression of NK1Rs in some subcortical brain regions. Combined, our findings suggest that while NK1R antagonism differentially influences alcohol- and cocaine-related behavior, this receptor mediates stress-induced seeking of both drugs.