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| Running for the Shelter of a Mother’s Little Helper: Behavioral and Pharmacological Determinants of Benzodiazepine Misuse |
| Sunday, May 26, 2024 |
| 8:00 AM–8:50 AM |
| Convention Center, 100 Level, 108 AB |
| Area: BPN; Domain: Applied Research |
| Chair: August F. Holtyn (National Institutes of Health) |
| CE Instructor: Sally L. Huskinson, Ph.D. |
| Presenting Author: SALLY L. HUSKINSON (University of Mississippi Medical Center) |
| Abstract: Benzodiazepines (BZs) are effective and safe when used appropriately, but their utility is limited by unwanted side effects like misuse and reduced safety when combined with other drugs. Individuals with substance-use disorders (SUDs) misuse BZs as much as 20x greater than the general population, and the rising number of overdose deaths attributed to BZs are largely driven by opioid co-administration. The work I will present is focused on behavioral and pharmacological determinants of BZ reinforcement using preclinical choice models in nonhuman primates. Our overall goal is to identify BZ-type ligands with reduced potential for misuse in naïve subjects as well as in polydrug situations. We have found that nonselective, partial-efficacy BZ ligands or those that lack intrinsic efficacy at α1-subunit containing GABAA (α1GABAA) receptors have reduced potential for misuse relative to traditional BZs. However, our data suggest that the degree to which these BZ-type ligands exhibit potential for misuse depends on the subject’s drug history. A key finding from our choice research is that efficacy at α1GABAA receptors may be necessary for self-administration of BZs in cocaine-experienced subjects but are not required for enhancement of cocaine choice. We currently are evaluating whether this pattern of effects is observed in individuals without prior drug experiences (i.e., in naïve subjects) or with other misused drugs, in particular opioids. The pharmacological mechanisms underlying outcomes based on past drug experience may involve (1) a differential role for α1GABAA receptors in reinforcement enhancing vs. reinforcing effects of BZs alone or (2) differences in overall intrinsic efficacy, irrespective of subtype selectivity. |
| Instruction Level: Intermediate |
| Target Audience: Basic and clinical students, researchers, and practitioners interested in substance use disorders |
| Learning Objectives: At the conclusion of this presentation, participants will be able to: 1) Explain how drug experience contributes to benzodiazepine reinforcement; 2) Describe how GABAA subunit selectivity and efficacy may contribute to benzodiazepine reinforcement; 3) Describe the strengths of using choice procedures to answer questions about behavioral and pharmacological mechanisms underlying benzodiazepine reinforcement. |
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| SALLY L. HUSKINSON (University of Mississippi Medical Center) |
 Dr. Sally Huskinson is currently an Associate Professor in the Division of Neurobiology and Behavior Research in the Department of Psychiatry and Human Behavior at the University of Mississippi Medical Center. As an undergraduate, she worked with Dr. Erin Rasmussen at Idaho State University where she earned her bachelor’s degree (2007) in psychology. She went on to earn her master’s (2011) and doctoral (2012) degrees in psychology at West Virginia University with the mentorship of Dr. Karen Anderson. In 2012, Dr. Huskinson went to the University of Mississippi Medical Center to complete a postdoctoral fellowship in behavioral pharmacology with Dr. William Woolverton until his untimely death in 2013. Dr. Huskinson finished her postdoctoral training with Drs. Kevin Freeman and James Rowlett, also at the University of Mississippi Medical Center where she currently resides. Her research is focused on substance use disorders with a particular interest in behavioral and pharmacological determinants of drug choice, the reinforcing effectiveness of drugs, and in creating more translationally relevant preclinical models of substance use disorders. |
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