Nonhuman animal models of substance use disorders: Translational value and utility to basic science

Background: The National Institute on Drug Abuse (NIDA) recently released a Request for Information (RFI) soliciting comments on nonhuman animal models of substance use disorders (SUD). Methods: A literature review was performed to address the four topics outlined in the RFI and one topic inspired by the RFI: (1) animal models that best recapitulate SUD, (2) animal models that best balance the trade-offs between resources and ecological validity, (3) animal models whose translational value are frequently misrepresented or overrepresented by the scientific community, (4) aspects of SLID that are not currently being modeled in animals, and (5) animal models that are optimal for examining the basic mechanisms by which drugs produce their abuse-related effects. Results: Models that employ response-contingent drug administration, use complex schedules of reinforcement, measure behaviors that mimic the distinguishing features of SUD, and use animals that are phylogenetically similar to humans have the greatest translational value. Models that produce stable and reproducible baselines of behavior, lessen the number of uncontrolled variables, and minimize the influence of extraneous factors are best at examining basic mechanisms contributing to drug reward and reinforcement. Conclusions: Nonhuman animal models of SLID have undergone significant refinements to increase their utility for basic science and translational value for SLID. The existing literature describes numerous examples of how these models may best be utilized to answer mechanistic questions of drug reward and identify potential therapeutic interventions for SUD. Progress in the field could be accelerated by further collaborations between researchers using animals versus humans.