Pramipexole‐induced Disruption of Behavioral Processes Fundamental to Intertemporal Choice

Abstract

Evaluating the effects of presession drug administration on intertemporal choice in nonhumans is a useful approach for identifying compounds that promote impulsive behavior in clinical populations, such as those prescribed the dopamine agonist pramipexole (PPX). Based on the results of previous studies, it is unclear whether PPX increases rats’ impulsive choice or attenuates aspects of stimulus control. The present study was designed to experimentally isolate behavioral processes fundamental to intertemporal choice and challenge them pharmacologically with PPX administration. In Experiment 1, the hypothesis that PPX increases impulsive choice as a result of enhanced sensitivity to reinforcer delays was tested and disconfirmed. That is, acute PPX diminished delay sensitivity in a manner consistent with disruption of stimulus control whereas repeated PPX had no effect on delay sensitivity. Experiments 2 and 3 elaborated upon this finding by examining the effects of repeated PPX on rats’ discrimination of response–reinforcer contingencies and reinforcer amounts, respectively. Accuracy of both discriminations was reduced by PPX. Collectively these results provide no support for past studies that have suggested PPX increases impulsive choice. Instead, PPX impairs stimulus control over choice behavior. The behavioral approach adopted herein could be profitably integrated with genetic and other biobehavioral models to advance our understanding of impulsive behavior associated with drug administration.

Pramipexole enhances disadvantageous decision-making: Lack of relation to changes in phasic dopamine release

“…Accordingly, PPX-treated rats engaged more in highly disadvantageous options (6.25% WP for two food pellets vs 100% WP for one food pellet, i.e., 1:8), and displayed a reduced proneness towards equally profitable alternatives (50% WP for two food pellets vs 100% for one food pellets, i.e., 1:1). The same PPX doses used in our study were found to increase impulsive choices in rats trained for delay-discounting tasks (Johnson et al, 2011; 2012; Madden et al, 2010), through impairments in the discrimination processes required for intertemporal choices (Johnson et al, 2013). Taken together, these data suggest that PPX may distort the representation of rewards and impair the ability to discern favorable from unfavorable contingencies.…”

Impulsive choice, alcohol consumption, and pre‐exposure to delayed rewards: II. Potential mechanisms

“…In this way, experiential variables like delay pre-exposure may be used as an experimental tool similar to pre-session drug administration in behavioral pharmacology (e.g., use of anxiolytic drugs to examine the role of anxiety in experimental paradigms). We note, however, that the varied behavioral effects of pharmacological treatment (e.g., on the reinforcing efficacy of food, discrimination of reinforcer contingencies, or motor behavior; Chu et al, 2014; Johnson, Stein, Smits, & Madden, 2013; Hoffman & Benninger, 1985) often make it difficult to attribute changes in behavior to precise mechanisms. In the abstract, delay pre-exposure may recruit fewer of these nuisance variables and would therefore be better suited for use in experimentation.…”

Dissecting drug effects in preclinical models of impulsive choice: emphasis on glutamatergic compounds

“…In a concurrent-chains procedure (Aparicio et al 2013; Aparicio et al 2015; Aparicio et al in press; Beeby and White 2013; Grace 2002; Johnson et al 2013; Oliveira et al 2014; Ong and White 2004; Orduña 2015; Orduña and Mercado 2017; Orduña et al 2013; Pitts and Febbo 2004), animals do not make a choice between rewards directly; instead, they make a choice between sources of reinforcement. Specifically, each trial is composed of an initial link and a terminal link.…”