Alcohol use disorder (AUD) is a significant public health concern, contributing to a myriad of social, psychological, and physiological issues. Despite substantial efforts within the alcohol research field, promising preclinical findings have failed to translate to clinical use, highlighting the necessity to develop safe and effective pharmacological probes with the ability to be used in preclinical and clinical research. Yohimbine, an α2 adrenergic receptor antagonist, is a well-validated pharmacological tool that has been widely employed in alcohol studies to evaluate noradrenergic activation. This scoping systematic review examines published literature in rodent and human studies involving the use of yohimbine relevant to alcohol research. We conducted a systematic literature review of MEDLINE, Embase, Web of Science Core Collection, CINAHL, PsycInfo, and Cochrane Central Register of Controlled Trials to identify: (1) Experimental Characteristics and Methodology, (2) Sex Differences, (3) Neurochemical Systems and Brain Regions, and (4) Discussion of Applications for Medication Development. Sixty-seven (62 preclinical and 5 clinical) studies were identified meeting the stated criteria, comprising extensive evidence supporting the use of yohimbine as a safe, titratable pharmacological agent for translational alcohol research. Support for the use of yohimbine as a fully translational tool, however, is hindered by limited available findings from human laboratory studies, as well as a dearth of studies examining sex differences in yohimbine’s mechanistic actions. Additional consideration should be given to further translational modeling, ideally allowing for parallel preclinical and clinical assessment of yohimbine, methodological assessment of neurochemical systems and brain regions.
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The authors also would like to thank the Brown University librarians, Laura Pavlech and Kelsey Sawyer, for constructing the systematic database searches. They would also like to thank Paul S. Soliman for his contributions during manuscript revision.
DEC is supported by the National Institute on Alcohol Abuse and Alcoholism (R01 AA027760 and Research Supplements to Promote Diversity in Health-Related Research). CLH-K is supported by the National Institute on Alcohol Abuse and Alcoholism (K01 AA023867; R01 AA026589; R01 AA027760; R21 AA027614) and by the National Institute of General Medical Sciences (NIGMS), Center of Biomedical Research Excellence (COBRE, P20 GM130414). RC is supported by the PRIN 2017SXEXT5, and NC is supported by the Hetzler Foundation (Grant 202213).
The authors declare no competing interests.
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Curley, D.E., Vasaturo-Kolodner, T.R., Cannella, N. et al. Yohimbine as a pharmacological probe for alcohol research: a systematic review of rodent and human studies. Neuropsychopharmacol. 47, 2111–2122 (2022). https://doi.org/10.1038/s41386-022-01363-9