Cocaine use disorder (CUD) is a disorder with high rates of relapse. Despite these high rates of relapse, there are no current FDA-approved medications to prevent cocaine relapse. Two factors that have been shown to influence rates of relapse are the trait of impulsivity and an individual’s level of reactivity to cocaine-related cues. Understanding the underlying neural mechanisms of how both impulsivity and reactivity to cocaine cues influence cocaine relapse could potentially lead to better pharmacotherapeutic treatment options to enhance recovery from CUD. To investigate this question, Dr. Kathryn Cunningham and her colleagues at the University of Texas Medical Branch in Galveston have used various rodent animal models of both impulsivity and cue reactivity. Through their research, Dr. Cunningham’s team has shown that there is a common serotonergic pathway that underlies the ability of both impulsivity and cue-reactivity to serve as relapse vulnerability factors in CUD. In a recently published study in the Journal of Pharmacology and Experimental Therapeutics, Dr. Cunningham’s group looked specifically at the role of the 5-HT2A receptor in impulsive action and cocaine cue reactivity in rats. To exam this, the team first tested the effects of the FDA-approved, 5-HT2A receptor antagonist pimavanserin on the 1-choice serial reaction time task (1-CSRT) of impulsive action. They obtained baseline impulsive action on the 1-CSRT task in a second group of rats who then were tested for cocaine cue reactivity by allowing them to acquire stable levels of cocaine self-administration followed by forced abstinence for either 1 day or 30 days. Either one day or 30 days after cocaine abstinence, rats were pretreated with various doses of pimavanserin or saline prior to measurement of levels of drug-seeking responses. Dr. Cunningham’s group found that pimavanserin suppressed impulsive action, and that the baseline level of impulsive action predicted the levels of cocaine cue reactivity on day 30 of abstinence. They also found that baseline levels of impulsive action predicted the effectiveness of pimavanserin to decrease the level of cocaine cue reactivity after 30 days of abstinence. These data are particularly exciting as indicating a potential serotonergic drug, which already has FDA approval, could be useful as a treatment for relapse in CUD. Also, the utility of the drug to treat cocaine relapse may be increased if the individual’s level of impulsivity is also considered in the treatment plan. This research conducted in a preclinical, animal model is an important step in the process of medications development for CUD. Given the extensive time and expense required to move novel compounds toward clinical use, animal studies are helpful in optimizing clinical trials with regard to assessment methods and endpoints that serve as indicators of success or failure. Dr. Cunningham has a long history of participation and leadership in CPDD. She won a travel award to attend the 1988 CPDD meeting and became a CPDD member in 1993, and became a fellow in 2007. Dr. Cunningham has chaired the Publications and Nominating Committees, served on the Board of Directors, and was elected CPDD President and member of the Executive Committee. She was awarded the CPDD Mentorship Award (2012) and the Marian W. Fischman Memorial Award (2013). Dr. Stairs has been a member of CPDD since 2010. He currently serves as a member on the Animals in Research Committee. By Dustin J Stairs, Ph.D., Animals in Research Committee Member.
