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.
Publication types
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Research Support, N.I.H., Intramural
MeSH terms
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Adrenergic alpha-2 Receptor Antagonists / pharmacology
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Alcohol-Related Disorders / drug therapy*
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Alcohol-Related Disorders / etiology
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Alcohol-Related Disorders / metabolism
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Animals
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Behavior, Addictive / chemically induced
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Behavior, Addictive / drug therapy*
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Behavior, Addictive / etiology
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Behavior, Addictive / metabolism
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Brain / metabolism
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Central Nervous System Depressants / administration & dosage
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Central Nervous System Depressants / pharmacology
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Cocaine / administration & dosage
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Cocaine / pharmacology
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Cocaine-Related Disorders / drug therapy*
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Cocaine-Related Disorders / etiology
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Cocaine-Related Disorders / metabolism
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Dopamine Uptake Inhibitors / administration & dosage
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Dopamine Uptake Inhibitors / pharmacology
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Ethanol / administration & dosage
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Ethanol / pharmacology
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Male
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Neurokinin-1 Receptor Antagonists / pharmacology*
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Piperidines / pharmacology*
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Rats
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Rats, Long-Evans
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Rats, Wistar
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Receptors, Neurokinin-1 / metabolism
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Recurrence
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Saccharin / administration & dosage
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Species Specificity
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Stress, Psychological / chemically induced
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Stress, Psychological / complications*
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Stress, Psychological / metabolism
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Yohimbine / pharmacology
Substances
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Adrenergic alpha-2 Receptor Antagonists
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Central Nervous System Depressants
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Dopamine Uptake Inhibitors
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N-((2-cyclopropoxy-5-(5-trifluomethyl)tetrazol-1-yl)benzyl)-2-phenylpiperidin-3-amine
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Neurokinin-1 Receptor Antagonists
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Piperidines
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Receptors, Neurokinin-1
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Yohimbine
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Ethanol
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Saccharin
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Cocaine