Dopaminergic lesions of the dorsolateral striatum in rats increase delay discounting in an impulsive choice task.

Stephanie E Tedford,Amanda L Persons,T Celeste Napier,David I Finkelstein

doi:10.1371/journal.pone.0122063

Abstract

Dysregulated dopamine transmission in striatal circuitry is associated with impulsivity. The current study evaluated the influence of dopaminergic inputs to the dorsolateral striatum on impulsive choice, one aspect of impulsive behavior. We implemented an operant task that measures impulsive choice in rats via delay discounting wherein intracranial self-stimulation (ICSS) was used as the positive reinforcer. To do so, rats were anesthetized to allow implanting of a stimulating electrode within the lateral hypothalamus of one hemisphere and bilateral dorsal striatal injections of the dopaminergic toxin, 6-OHDA (lesioned) or its vehicle (sham). Following recovery, rats were trained in a delay discounting task wherein they selected between a small ICSS current presented immediately after lever pressing, and a large ICSS current presented following a 0 to 15s delay upon pressing the alternate lever. Task acquisition and reinforcer discrimination were similar for lesioned and sham rats. All rats exhibited an initial preference for the large reinforcer, and as the delay was increased, preference for the large reinforcer was decreased indicating that the subjective value of the large reinforcer was discounted as a function of delay time. However, this discounting effect was significantly enhanced in lesioned rats for the longer delays. These data reveal a contribution of dopaminergic inputs to the dorsolateral striatum on impulsive choice behavior, and provide new insights into neural substrates underlying discounting behaviors.

Highlights

Impulsivity is a general term that umbrellas many aspects of impulsive behavior, including suboptimal risk/reward, effort-based, and delay-based decision-making
Rats with intra-dorsolateral striatum (DLS) injections of 6-OHDA displayed a significant decrease (~51%) in tyrosine hydroxylase (TH)-ir+ cells within this nigral subregion compared to shams (t(10) = 3.8, p = 0.003), indicating that lesions of the DLS caused retrograde loss of dopaminergic cell bodies located in the substantia nigra pars compacta (SNpc)
We found that dopaminergic lesions of the DLS decreased preference for the delayed large reinforcer (LR) at a faster rate than sham controls; discounting was enhanced

Summary

Introduction

Impulsivity is a general term that umbrellas many aspects of impulsive behavior, including suboptimal risk/reward, effort-based, and delay-based decision-making. Decision-making involves complex, reward-mediated processes that are sensitive to several weighted factors, including the probability, workload, and delay of a potential reward. A facet of delaybased decision-making, can be studied using delay discounting paradigms wherein subjects select between an immediate, often smaller reward, and a delayed, often larger reward. As the delay towards delivery of the large reward is increased, the subjective value of the reward often. Dorsolateral Striatal Lesions Increase Impulsivity is decreased (i.e., discounted), and preference is shifted to the immediate, smaller reward. Impulsive choice is considered to reflect preference for the immediately available small reward without appropriate consideration for the larger, albeit delayed, reward. Determining the neural anatomical substrates of impulsive choice is a critical aspect of understanding and subsequently treating these brain diseases

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Conclusion