William L. Woolverton: A case history in unraveling the behavioral pharmacology of stimulants

Abstract

Clinical findings suggest that the most promising strategy for cocaine addiction is a combination of indirect-acting monoamine agonists with some form of behavioral intervention. This approach can be traced back to preclinical research, some of which was conducted by William L. Woolverton. The goal of this brief review is to provide readers with an appreciation for the experimental breadth involving both behavior and pharmacology that encompassed Woolverton's amazing career, from the evaluation of abuse liability of drugs to the use of complex behavioral contingencies to better model the human condition. We begin with Woolverton's research using simple and complex schedules of reinforcement to evaluate abuse liability and how that has impacted current animal models. We also discuss his use of cocaine vs. food choice schedules of reinforcement as a model to evaluate potential medications for treating cocaine use disorders. Woolverton concluded that drug taking behavior was not “impulsive” and “out of control” as has often been proposed, but rather directly determined by the environmental contingencies and the context of its availability, providing a nuanced understanding of drug-behavior interactions.

Levamisole enhances the rewarding and locomotor-activating effects of cocaine in rats

“…The ability of cocaine to produce rewarding effects in place conditioning assays and stimulant effects in locomotor and motility assays is established across different species, including rats, mice and invertebrates (Nader et al, 2014; Tallarida et al, 2014; Pagan et al, 2008, 2009, 2013; Rawls et al, 2010, 2011; Aguilar et al, 2009; Huber et al, 2011). In contrast, for LVM, its in vivo profile remains incomplete despite being synthesized by Janssen Pharmaceuticals almost five decades ago (Raeymakers et al, 1967).…”