Association for Behavior Analysis International

The Association for Behavior Analysis International® (ABAI) is a nonprofit membership organization with the mission to contribute to the well-being of society by developing, enhancing, and supporting the growth and vitality of the science of behavior analysis through research, education, and practice.

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11th International Conference; Dublin, Ireland; 2022

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Symposium #122
Behavior Analysis in Drug Discovery and Evaluation
Saturday, September 3, 2022
2:00 PM–3:50 PM
Meeting Level 1; Liffey Meeting 1
Area: BPN/EAB; Domain: Basic Research
Chair: Chris E. Hughes (University of North Carolina Wilmington)
Discussant: Jack Bergman (Harvard Medical School - McLean Hospital)
Abstract: Behavior analysis research plays an important role in the discovery and evaluation of psychoactive drugs and the development of novel pharmacotherapies. This symposium covers several lines of research investigating the behavioral effects of drugs and demonstrates approaches for rigorously characterizing drug effects in vivo. The first presenter (Dr. Vanessa Minervini) will describe the development of a choice procedure for studying the reinforcing and punishing effects of drugs and drug mixtures. The second presenter (Dr. Brian Kangas) will outline a translational approach to accelerate medications development for neuropsychiatric disorders involving anhedonia. The third presenter (Dr. Ray Pitts) will discuss how behavioral procedures can be adapted to allow for parametric examination of effects of the reinforcement dimensions involved in impulsive choice. The fourth presenter (Dr. David Maguire) will review preclinical studies demonstrating the therapeutic potential of a long-acting mu opioid receptor antagonist for treating opioid use disorder. Dr. Jack Bergman will serve as the discussant. Taken together, these presentations will provide a sampling of contemporary research in behavioral pharmacology, while highlighting the complex interactions among drugs, behavior, and environment and underscoring the value of behavioral research for developing novel, safe, and effective therapeutics.
Instruction Level: Basic
Keyword(s): Behavioral pharmacology, Drug discovery, Psychoactive drugs, Translational research
 
Reinforcing and Punishing Effects of Drugs and Drug Mixtures in Rats Responding Under a Choice Procedure
VANESSA MINERVINI (Creighton University)
Abstract: Opioids are the gold standard for treating pain despite the adverse effects (e.g., abuse) of these drugs, and safer options for pain management are needed. Combining opioids with drugs that are not reinforcing (and perhaps punishing), might reduce adverse effects while maintaining adequate pain relief. This study compared the effects of the opioid remifentanil and a drug with well-established punishing effects, histamine, alone and in mixtures to test the hypothesis that remifentanil/histamine mixtures are less reinforcing compared with remifentanil alone. Rats chose between a pellet alone and a pellet + an intravenous infusion. Histamine alone dose-dependently decreased responding for a pellet + an infusion; conversely, rats chose a pellet + remifentanil in a dose-dependent manner. Responding for remifentanil/histamine mixtures generally was not different from the constituent dose of remifentanil in the mixture but was different from the constituent dose of histamine. A mixture containing 0.001 mg/kg/infusion remifentanil and 3.2 mg/kg/infusion histamine was different from the constituent doses but not saline. Reinforcing doses of remifentanil combined with punishing doses of histamine can yield mixtures that are neither reinforcing nor punishing, and this study offers a “proof-of-principle” for using drug mixtures to decrease the dose of the opioid and avoid adverse effects.
 
Signal Detection Theory in Neuropsychiatric Medications Development
BRIAN D. KANGAS (Harvard Medical School)
Abstract: Anhedonia, the loss of reactivity to previously reinforcing stimuli, is a core symptom of several diverse neuropsychiatric conditions, including major depressive disorder, bipolar disorder, post-traumatic stress disorder, schizophrenia, and substance use disorders. Unfortunately, despite its transdiagnostic prevalence, no approved therapeutics exist to treat anhedonia. This presentation will review our recent studies exposing humans, rodents, and nonhuman primates to probabilistic reinforcement schedules and use of signal detection metrics to objectively quantify their reactivity to reward. In these computerized tasks, subjects make visual discriminations and asymmetric probabilistic contingencies are arranged such that correct responses to one alternative are rewarded more often (rich) than correct responses to the other (lean). Under these conditions, both healthy humans and laboratory animals consistently develop a response bias in favor of the rich alternative. However, patients with neuropsychiatric disorders often exhibit blunted biases, which correlate with current, and predict future, anhedonia. Likewise, laboratory animals exposed to early-life adversity or chronic stress also display blunted biases. Moreover, pharmacological challenges with candidate therapeutics known to enhance hedonic tone have produced similar desirable outcomes across species. Taken together, this quantitative framework offers a highly translational approach to accelerate medications development for neuropsychiatric disorders involving anhedonia.
 
An Efficient Method for Studying Reinforcement Mechanisms Controlling Impulsive Choice for Use in Behavioral Neuroscience
RAYMOND C. PITTS (University of North Carolina Wilmington), Ryan Charles Blejewski (University of North Carolina Wilmington), Jeremy Saul Langford (West Virginia University), Justin T Van Heukelom (University of North Carolina Wilmington), Chris E. Hughes (University of North Carolina Wilmington)
Abstract: Although procedures originating within the experimental analysis of behavior commonly are used in behavioral neuroscience to produce behavioral endpoints, they less often are used to analyze the behavioral processes involved, particularly at the level of individual organisms (see Soto, 2020). Concurrent-chains procedures have been used extensively to study choice and to quantify relations between various dimensions of reinforcement and preference. Unfortunately, parametric analysis of those relations using traditional steady-state, single-subject experimental designs can be time-consuming, often rendering these procedures impractical for use in behavioral neuroscience/behavioral pharmacology. The purpose of this talk is to describe how concurrent-chains procedures can be adapted to allow for parametric examination of effects of the reinforcement dimensions involved in impulsive choice (magnitude and delay) within experimental sessions in rats. Data are presented indicating that this procedure can produce relatively consistent within-session estimates of sensitivity to reinforcement in individual subjects, and that these estimates can be affected by drug administration (data are presented for the opioid drug, oxycodone). It is suggested that this type of procedure offers a promising approach to the study of neurobiological mechanisms of impulsive choice in individual organisms, which could facilitate a more fruitful relationship between behavior analysis and behavioral neuroscience.
 
Preclinical Evaluation of Methocinnamox as a Potential Treatment for Opioid Use Disorder
DAVID R. MAGUIRE (University of Texas Health Science Center at San Antonio), Charles Patrick France (University of Texas Health Science Center at San Antonio)
Abstract: Opioid abuse remains a serious public health challenge despite the availability of effective medications such as methadone, buprenorphine, naltrexone, and naloxone. Methocinnamox (MCAM) is a selective, long-acting mu opioid receptor antagonist that reliably attenuates abuse- and overdose-related effects of opioids such as heroin and fentanyl, suggesting it could be a safe and effective treatment for opioid use disorder and opioid overdose. Preclinical studies demonstrating the therapeutic potential of MCAM will be reviewed, focusing on effects of MCAM on opioid self-administration in nonhuman subjects. Acute and daily MCAM treatment produces selective and long-lasting blockade of fentanyl self-administration in a manner consistent with a non-competitive (irreversible) interaction of MCAM and mu opioid receptors. MCAM also attenuates other adverse effects of opioids (e.g., ventilatory depression), with protection lasting for days to weeks following a single injection. Taken together, these results indicate that MCAM could be a safe and effective treatment for opioid use disorder and opioid overdose. In addition to reporting recent exciting results, this talk will highlight behavior analytic principles and procedures utilized to characterize this potentially life-saving drug.
 

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