Journal article

Acetylcholine Muscarinic M-4 Receptors as a Therapeutic Target for Alcohol Use Disorder: Converging Evidence From Humans and Rodents

Leigh C Walker, Alice E Berizzi, Nicola A Chen, Patricia Rueda, Victoria M Perreau, Katherine Huckstep, Jirawoot Srisontiyakul, Piyarat Govitrapong, Xiaojian Jia, Craig W Lindsley, Carrie K Jones, Darren M Riddy, Arthur Christopoulos, Christopher J Langmead, Andrew J Lawrence

Biological Psychiatry | ELSEVIER SCIENCE INC | Published : 2020

Abstract

BACKGROUND: Alcohol use disorder (AUD) is a major socioeconomic burden on society, and current pharmacotherapeutic treatment options are inadequate. Aberrant alcohol use and seeking alters frontostriatal function. METHODS: We performed genome-wide RNA sequencing and subsequent quantitative polymerase chain reaction and receptor binding validation in the caudate-putamen of human AUD samples to identify potential therapeutic targets. We then back-translated our top candidate targets into a rodent model of long-term alcohol consumption to assess concordance of molecular adaptations in the rat striatum. Finally, we adopted rat behavioral models of alcohol intake and seeking to validate a potenti..

View full abstract

Grants

Awarded by National Institute of Alcohol Abuse and Alcoholism of the National Institutes of Health


Awarded by National Health and Medical Research Council


Awarded by Thai Royal Golden Jubilee PhD Program


Funding Acknowledgements

Human tissues were received from the New South Wales Tissue Resource Centre at the University of Sydney that is supported by the University of Sydney. Research reported in this article was supported by the National Institute of Alcohol Abuse and Alcoholism of the National Institutes of Health (Grant No. R28AA012725). The content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health. This research was also supported by a National Health and Medical Research Council project grant (Grant No. 1120576 [to AJL and CJL]), of which AJL is a principal research fellow (Grant No. 1116930). JS was supported by the Thai Royal Golden Jubilee PhD Program (Grant No. PHD/0253/2552) and by Mahidol University.