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

Neurokinin-I receptors (NKIRs) have been shown to mediate alcohol and opiate, but not cocaine reward in rodents. We recently reported that NKIR 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 NKIR in reinstatement of cocaine seeking. Here, we explored the effect of the NKIR 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 NKIR antagonism than Wistar rats. Accordingly, Long-Evans rats exhibit differences in the expression of NKIRs in some subcortical brain regions. Combined, our findings suggest that while NKIR antagonism differentially influences alcohol and cocaine-related behavior, this receptor mediates stress-induced seeking of both drugs.