The neurokinin-1 receptor antagonist L822429 suppresses stress-induced reinstatement and escalated alcohol consumption in rats

Wednesday, October 26, 2011 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center	NIAAA	NEURO/BEHAV/SENSYS-28

* FARE Award Winner

Authors

• J Schank
• K Rowe
• R Damadzic
• K Cheng
• A Thorsell
• K Rice
• M Heilig

Abstract

The neurokinin-1 receptor (NK1R) serves as the preferred target of the neuropeptide substance P (SP). The SP/NK1 system has been shown by our lab and others to be involved in alcohol-related behaviors. In these studies we used the NK1R antagonist L822429 to examine the role of the SP/NK1 system in alcohol self-administration, reinstatement of alcohol seeking, and escalated consumption in an alcohol preferring rat line. We found that L822429 had no effect on baseline alcohol self-administration or cue-induced reinstatement, but dose-dependently blocked stress-induced reinstatement in normal rats. We also measured c-fos expression during stress-induced reinstatement and found that L822429 blocked the stress-induced increase in c-fos protein in the dorsal raphe and nucleus accumbens. Given the activity profile of other anti-stress drugs, we hypothesized that NK1R antagonists may have a more potent effect on self-administration in models of escalated consumption. To assess this possibility we used the alcohol preferring P rat, and found that excessive alcohol self-administration in this line was selectively reversed by pretreatment with L822429. These results suggest that the SP/NK1 system plays a significant role in excessive alcohol consumption, and further indicate the NK1R as a particularly useful target for the development of medications to treat alcoholism.

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