Behavioral Mechanisms of Pramipexole-Induced Impulsivity: Discrimination Processes Underlying Decision-Making

Abstract

Faced with an intertemporal choice, an organism that chooses a “smaller-sooner” reinforcer over a “larger-later” reinforcer is said to behave impulsively. Individual differences in intertemporal choice are effectively modeled by generalized matching law and delay discounting equations that incorporate parameters corresponding to behavioral processes such as sensitivity to reinforcer amount or delay. By simulating changes in these processes and identifying conditions under which impulsive choice is likely to result, researchers are in a position to anticipate and examine potential behavioral mechanisms underlying clinical instances of impulsivity. Pramipexole, a dopamine agonist medication, is associated with reports of impulsive behavior in populations prescribed the drug, as well as in experimental subjects administered the compound prior to intertemporal choice sessions, although the latter findings are mixed. The present set of experiments was designed (a) to systematically replicate conditions under which pramipexole increased impulsive choice, but also nonspecifically disrupted behavior, and (b) to elucidate behavioral mechanisms of pramipexole-induced impulsivity in rats. In Chapter 2, a behavioral task used previously by researchers reporting a nonspecific effect of pramipexole was modified to include procedural controls common in the intertemporal choice literature (centering response, no-delay sessions). In accord with previous findings, acute pramipexole nonspecifically disrupted choice behavior, while chronic pramipexole partially remediated elements of the disruption (i.e., decrease in initial-block choice). In Chapter 3, three experiments targeted behavioral processes critical for intertemporal choice. Experiment 1 evaluated the acute and chronic effects of pramipexole on rats’ sensitivity to relative reinforcer delays in a concurrent-chains procedure. Contrary to the predicted effect, the drug decreased this measure, indicating the possibility of impaired stimulus control. Experiments 2 and 3 assessed the drug effect on discrimination of response-reinforcer contingencies and of reinforcer amounts, respectively, and revealed deficits in accuracy of similar magnitude across both preparations. Collectively, the results of these experiments suggest that previous findings of pramipexole-induced impulsivity and nonspecific disruption of behavior can be explained as impairments in discrimination processes required for intertemporal choice. Although the generality of the present findings may be limited to experimental settings with nonhumans, they demonstrate the utility of quantitatively modeling impulsivity

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