Neurokinin 1 receptor blockade in the medial amygdala attenuates alcohol drinking in rats with innate anxiety but not in Wistar rats

Background and Purpose

Substance P and its preferred neurokinin receptor NK₁ 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 NK₁ 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. NK₁ 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.

DOI: 10.1111/bph.13280

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