Needed: mouse/human cross validation of reinstatement/relapse models (and drug reward models) to model human substance abuse vulnerability allelic variants.

Abstract

Classical human genetic studies document strong complex genetic contributions to abuse of multiple addictive substances. Recent molecular genetic studies have uncovered gratifyingly reproducible human allelic variants that contribute to this overall human genetic vulnerability to addictions in several populations (reviewed in Uhl et al. 1995, 2002; Uhl 1999). Behavioral assessments and gene variations identified in human studies can be studied in mice, where experimental control of genetic background and behavioral histories can produce power to isolate the effects of single gene variants that may not be available in human studies. Working mouse models are thus needed to be able to define the phenotypes that each human addiction vulnerability allelic variant can produce. Validated relapse/reinstatement mouse models for studies of human addiction vulnerability genetics could provide a potentially powerful pairing with better-studied models for acute drug reward.