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.
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Acknowledgements
This work was funded by the National Institute on Alcohol Abuse and Alcoholism Intramural Research Program, the National Institute on Drug Abuse Intramural Research Program, and the National Institute of Drug Abuse (RO1DA027535 to DW), and Grant K99AA021805 (JRS). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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Schank, J., King, C., Sun, H. et al. The Role of the Neurokinin-1 Receptor in Stress-Induced Reinstatement of Alcohol and Cocaine Seeking. Neuropsychopharmacol 39, 1093–1101 (2014). https://doi.org/10.1038/npp.2013.309
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DOI: https://doi.org/10.1038/npp.2013.309
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