|The Importance of Replication in Developing Valid Animal Models of Behavioral Disorders
|Saturday, May 25, 2019
|5:00 PM–5:50 PM
|Swissôtel, Concourse Level, Zurich BC
|Area: EAB/DDA; Domain: Translational
|Chair: Marc N. Branch (University of Florida)
|Abstract: Despite the many genetic and ontogenetic animal models of neurodevelopmental disorders (e.g., intellectual disabilities autism, and attention deficit disorder) available for research none have led to novel treatments. Repeatedly, drugs have been shown to "rescue" behavioral abnormalities associated with these models, only to fail in human, clinical trials. This poor predictive validity of current models has led The National Institutes of Health to make developing new animal models of neurodevelopmental disorders a priority area. One source of error may be the “behavioral assays” used to assess treatments. Current measures of behavior are selected for face validity, and their relation to clinical behaviors is unknown. Behavior analysis explicitly establishes cross-species generality including to humans. Predictive validity is established by showing that a manipulation will have the same outcome in rats, pigeons, non-human primates, and humans. Dr. Hughes presents data from behavior pharmacology - the gold standard for predictive validity of animal models. Dr. Perone discusses the critical component of predictive validity – interspecies generality of processes and methods. Dr. Williams presents an example of interspecies generality research pertaining to neurodevelopmental disorders.
|Instruction Level: Advanced
|Keyword(s): Animal Models, Developmental Dissabilies, Drugs, Human Subjects
|Replication and Replication Failure in the Search for Fundamental Behavioral Processes
|MICHAEL PERONE (West Virginia University)
|Abstract: This talk will discuss strategies for addressing replication successes and failures and illustrate how our response to the failures plays a critical role in advancing our understanding of fundamental behavioral processes. A behavioral process is fundamental if it transcends species boundaries, and precise expressions of fundamental processes are – by their very nature – high in generality and predictive value. The experimental analysis of behavior is devoted to the discovery and articulation of fundamental processes. Achieving this goal depends on experiments that focus on environmental determinants of behavior at the level of the individual organism, rigorous methods with the highest possible internal validity, and both direct and systematic replication. Replication failures are likely, especially when procedures from the animal lab are translated to humans, and they should be welcome. If the experiments are internally valid, the failures are as informative as the successes because the failures point the way to unknown or uncontrolled factors involved in the process of interest. When these factors are identified and controlled, our expressions of the behavioral process will be precise, general, and predictive.
Behavioral Pharmacology: An Animal-Model Success Story
|Christine Hughes (University of North Carolina Wilmington), MARC N. BRANCH (University of Florida)
Behavioral pharmacology is often described as the merging of the fields of behavior analysis and pharmacology. As a result, our principles and methodologies were brought to bear on understanding both the pharmacological and the behavioral functions of drugs. The utilization of a steady-state research strategy in individual subjects helped to reconcile some views that drug effects were intrinsically variable. Conceptualizing drugs as reinforcing and discriminative stimuli helped not only to develop reliable laboratory animal models, but also, to conceptualize treatment of behavioral disorders both in terms of psycho- and pharmacotherapy. In this presentation, I will present a general overview of the tenets of behavioral pharmacology and discuss a brief history of the use of some of the animal models that have been shown to have high predictive validity including current models of impulsive behavior.
|Reverse Translation of Problem Behaviors in Developmental Disabilities Through Replication in Animal and Human Subjects
|DEAN C. WILLIAMS (University of Kansas)
|Abstract: Disruptive and destructive behaviors present a major and persistent problem in people with developmental disabilities (DD). Applied behavior analysis takes a functional approach aimed at treating specific problem behaviors regardless of subjects’ diagnosis. Other disciplines take a medical model and focus on behaviors as symptoms of the underlying neurodevelopmental disabilities. The Incidences of problem behaviors varies across DD syndromes with known genetic etiologies indicating a potential biological underpinning for these behaviors. A major area of research in DD involves animal models of specific syndromes to understand biological mechanisms and develop new treatments, but to date have not succeeded in either goal. Current animal models use behavioral “assays” based on formal similarity to diagnostic behaviors (face validity). The literature acknowledges this practice is unsatisfactory, but there is a lack of reverse translation of the clinical behaviors to basic processes that can be reproduced in animals. In this paper, we present replication of functional relations from animal and human subjects related to conditions that produce maladaptive escape, response disruption, and aggressive behaviors. We argue that the animal and human results are due to similar behavioral processes enhancing the predictive potential of treatments derived from the animal models.