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Neurokinin 1 receptor blockade in the medial amygdala attenuates alcohol drinking in rats with innate anxiety but not in Wistar rats
Author(s) -
Ayanwuyi Lydia O,
Stopponi Serena,
Ubaldi Massimo,
Cippitelli Andrea,
Nasuti Cinzia,
Damadzic Ruslan,
Heilig Markus,
Schank Jesse,
Cheng Kejun,
Rice Kenner C,
Ciccocioppo Roberto
Publication year - 2015
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.13280
Subject(s) - amygdala , tachykinin receptor 1 , self administration , medicine , elevated plus maze , endocrinology , alcohol use disorder , receptor , alcohol , anxiety , psychology , receptor antagonist , antagonist , pharmacology , neuropeptide , substance p , psychiatry , chemistry , biochemistry
Background and Purpose Substance P and its preferred neurokinin receptor NK 1 have been implicated in stress and anxiety and have been proposed as possible therapeutic targets for the treatment of anxiety/depression. Attention is also being focused on the role this neuropeptide system may play in drug addiction, because stress‐related mechanisms promote drug abuse. Experimental Approach The effects of the rat‐specific NK 1 receptor antagonist, L822429, on alcohol intake and seeking behaviour was investigated in genetically selected Marchigian Sardinian alcohol preferring rats. These rats demonstrate an anxious phenotype and are highly sensitive to stress and stress‐induced drinking. Key Results Systemic administration of L822429 significantly reduced operant alcohol self‐administration in Marchigian Sardinian alcohol preferring rats, but did not reduce alcohol self‐administration in stock Wistar rats. NK 1 receptor antagonism also attenuated yohimbine‐induced reinstatement of alcohol seeking at all doses tested but had no effect on cue‐induced reinstatement of alcohol seeking. L822429 reduced operant alcohol self‐administration when injected into the lateral cerebroventricles or the medial amygdala. L822429 injected into the medial amygdala also significantly reduced anxiety‐like behaviour in the elevated plus maze test. No effects on alcohol intake were observed following injection of L822429 into the dorsal or the ventral hippocampus. Conclusions and Implications Our results suggest that NK 1 receptor antagonists may be useful for the treatment of alcohol addiction associated with stress or comorbid anxiety disorders. The medial amygdala appears to be an important brain site of action of NK 1 receptor antagonism.