|Behavioral and Pharmacological Determinants of Impulsive Behavior and Attending: A Search for Mechanism
|Saturday, May 25, 2019
|4:00 PM–4:50 PM
|Swissôtel, Lucerne Ballroom Level, Alpine 1/2
|Area: BPN/EAB; Domain: Basic Research
|Chair: Christine E. Hughes (University of North Carolina Wilmington)
|CE Instructor: Christine E. Hughes, Ph.D.
Impulsive behavior has been termed a “transdisease” process because it is a key component in numerous clinical disorders. Deficits in attending certainly qualify as well. Experimental measures of both are grounded in choice, one of the two conference themes in 2019. These processes will be examined from multiple perspectives but all with the goal of understanding their behavioral and pharmacological mechanisms and correlates. The first paper will examine correlates among attending, impulsive behavior, and short-term remembering in a mouse model of Alzheimer’s disease. The second will examine how reinforcement magnitude and probability influence methylphenidate’s effects on risky decision making. The third will examine the role of baseline levels of impulsivity in determining the effect of d-amphetamine. Together, these papers will present, in a single setting, these multifaceted concepts using different experimental models. They will also summarize how impulsive behavior and attending relate to other important phenomena such as short-term remembering dementia, and the broader context in which the choices are made.
|Instruction Level: Intermediate
|Keyword(s): Alzheimer's Disease, Attention, Delay Discounting, Psychomotor Stimulants
Scientists and practitioners interested in current thinking about the determinants of impulsive behavior and attending. While the studies are basic they have very clear transnational and applied implications.
|Learning Objectives: Learn how the baseline rate of discounting influences the effects of drugs used to manage impulsive behavior. Learn how attending and remembering are related in an experimental model of Alzheimer's disease Learn how delay discounting interacts with
Longitudinal Assessment of Short-Term Remembering and Attending in a Mouse Model of Alzheimer’s Related Amyloidosis
|PAUL SOTO (Louisiana State University), Breanna Harris (Texas Tech University)
In 2017, an estimated five million Americans were living with Alzheimer’s disease (AD), a progressive neurological disease that interferes with cognitive function, reduces quality of life, and is a significant economic burden to society. There is a need for pharmacotherapeutics for AD-associated cognitive impairment, the development of which requires preclinical models of AD-associated cognitive impairment. The aim of this study was to evaluate cognitive impairment in a mouse model of AD-associated amyloidosis. APPswe/PS1dE9 double transgenic (Tg) male and female mice and non-transgenic (non-Tg) littermates were trained on a delayed-matching-to-position (DMTP) or 3-choice serial reaction time (3CSRT) task. Mice were tested either continuously or intermittently from approximately 2 to 18 months of age. In the DMTP task, accuracy declined with the delay between sample lever presentation and choice opportunity although there was little evidence of between-genotype differences in performance. In the 3CSRT task, accuracy declined with duration of the signal stimulus and impulsive responses decreased as the time before the signal stimulus increased, but there were no between-genotype differences in accuracy, impulsive responses, or omissions. Potential factors contributing to lack of impairment in DMTP/3CSRT performance in the APPswe/PS1dE9 double mouse model of AD-associated amyloidosis will be discussed.
|Methylphenidate Alters Sensitivity to Reinforcement Amount, Delay, and Probability: Implications for Impulsive/Risky Choice
|Jeremy Langford (University of North Carolina Wilmington), Christine E. Hughes (University of North Carolina Wilmington), RAYMOND C. PITTS (University of North Carolina Wilmington)
|Abstract: There has been growing interest in studying effects of drugs on impulsive and risky decision making. Identifying the relevant dimensions of reinforcement involved in these choices and quantifying the impact of drugs on control of choice by those dimensions might prove useful. The purpose of this study was to investigate drug-induced changes in control by reinforcement amount and delay in combination (Experiment 1) and reinforcement amount and probability in combination (Experiment 2) in a laboratory model of choice. In both experiments, pigeons responded on a rapid-acquisition, concurrent-chains procedure in which both terminal-link parameters of reinforcement alternated independently and pseudo-randomly across sessions; in some sessions both parameters favored one response key (dominated sessions); in other sessions each parameter favored a different key (tradeoff sessions). In both experiments, Initial-link response allocation tracked the four different terminal-link arrangements in a manner indicating independent and additive contributions by both reinforcement parameters (as assumed by the Generalized Matching Law). Methylphenidate reliably attenuated sensitivity to all dimensions of reinforcement at doses that did not substantially alter bias or initial-link response rates. Implications for theories of choice and for identifying behavioral mechanisms of drug action on impulsive and risky choice are discussed.
Baseline Dependency and Delay Discounting
|M. CHRISTOPHER NEWLAND (Auburn University), Blake A. Hutsell (Eastern Carolina University), Derek Pope (Virginia Tech Carilion Research Institute)
Psychomotor stimulants can increase activity and impulsivity under non-clinical conditions but have the opposite effects in individuals with ADHD. This suggests a baseline-dependency in which a drug stabilizes an aspect of behavior by decreasing high-probability events while increasing low-probability events. Baseline-dependent effects on delay-discounting can be examined experimentally using inbred mouse strains that have different behavioral profiles and also by arranging conditions that yield different levels of discounting. BALB/c mice show greater sensitivity to reinforcer magnitude and delay than C57Bl/6 mice, making these two strains ideal subjects for examining baseline dependency on both measures. The presence of delay-specific stimuli can also influence the degree of magnitude- and delay sensitivity. These gene X environment interactions can be exploited to identify a common basis for the effects of a psychomotor stimulant. Across strains and stimulus conditions, d-amphetamine decreases both magnitude and delay sensitivity when they are high and increases it when it is low. The effects of this drug, both in an experimental model and in clinical settings, depends critically upon the baseline conditions under which behavior is maintained.