title: 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.
authors.affiliation: Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Jesse R
authors.initials: JR
authors.lastname: Schank
authors.affiliation: Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Courtney E
authors.initials: CE
authors.lastname: King
authors.affiliation: Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.affiliation: Chemical Biology Branch, National Institute on Alcohol Abuse and Alcoholism and National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Kejun
authors.initials: K
authors.lastname: Cheng
authors.affiliation: Chemical Biology Branch, National Institute on Alcohol Abuse and Alcoholism and National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Kenner C
authors.initials: KC
authors.lastname: Rice
authors.affiliation: Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Markus
authors.initials: M
authors.lastname: Heilig
authors.affiliation: Department of Human Genetics, Emory University, Atlanta, GA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Weinshenker
authors.affiliation: Department of Human Genetics, Emory University, Atlanta, GA, USA.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Schroeder
mesh_terms: D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D019973:Alcohol-Related Disorders / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D000818:Animals; D016739:Behavior, Addictive / Q000139:chemically induced / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D012008:Recurrence; D012439:Saccharin / Q000008:administration & dosage; D013045:Species Specificity; D013315:Stress, Psychological / Q000139:chemically induced / Q000150:complications* / Q000378:metabolism; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D002492:Central Nervous System Depressants; D018765:Dopamine Uptake Inhibitors; C532739:N-((2-cyclopropoxy-5-(5-trifluomethyl)tetrazol-1-yl)benzyl)-2-phenylpiperidin-3-amine; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D018040:Receptors, Neurokinin-1; D015016:Yohimbine; D000431:Ethanol; D012439:Saccharin; D003042:Cocaine