Assessment of reward responsiveness in the response bias probabilistic reward task in rats: implications for cross-species translational research

A Der-Avakian,M S D'Souza,A Markou,D A Pizzagalli

doi:10.1038/tp.2013.74

Abstract

Mood disorders, such as major depressive disorder, are characterized by abnormal reward responsiveness. The Response Bias Probabilistic Reward Task (hereafter referred to as probabilistic reward task (PRT)) quantifies reward responsiveness in human subjects, and an equivalent animal assessment is needed to facilitate preclinical translational research. Thus, the goals of the present studies were to develop, validate and characterize a rat analog of the PRT. Adult male Wistar and Long–Evans rats were trained in operant testing chambers to discriminate between two tone stimuli that varied in duration (0.5 and 2 s). During a subsequent test session consisting of 100 trials, the two tones were made ambiguous (0.9 and 1.6 s) and correct identification of one tone was reinforced with a food pellet three times more frequently than the other tone. In subsequent experiments, Wistar rats were administered either a low dose of the dopamine D2/D3 receptor agonist pramipexole (0.1 mg kg−1, subcutaneous) or the psychostimulant amphetamine (0.5 mg kg−1, intraperitoneal) before the test session. Similar to human subjects, both rat strains developed a response bias toward the more frequently reinforced stimulus, reflecting robust reward responsiveness. Mirroring prior findings in humans, a low dose of pramipexole blunted response bias. Moreover, in rats, amphetamine potentiated response bias. These results indicate that in rats, reward responsiveness can be quantified and bidirectionally modulated by pharmacological manipulations that alter striatal dopamine transmission. Thus, this new procedure in rats, which is conceptually and procedurally analogous to the one used in humans, provides a reverse translational platform to investigate abnormal reward responsiveness across species.

Highlights

Deficits in reward processing characterize a broad array of neuropsychiatric disorders, including major depressive disorder (MDD), substance abuse and schizophrenia.[1]
Using procedures that are analogous to the human Response Bias PRT,[5] we developed a new behavioral task to assess reward responsiveness in rats
Reward responsiveness reflects the modulation of a behavioral choice as a function of prior reinforcement history

Summary

Introduction

Deficits in reward processing characterize a broad array of neuropsychiatric disorders, including major depressive disorder (MDD), substance abuse and schizophrenia.[1]. The use of subjective assessments that rely on an individual’s ability to recall past or imagine hypothetical pleasurable experiences is impossible to model in laboratory animals, limiting the potential impact of animal research on the discovery of new treatments for reward-related deficits in neuropsychiatric disorders To address this issue, clinical researchers have begun to develop objective, laboratory-based tasks to investigate discrete reward processes. Clinical researchers have begun to develop objective, laboratory-based tasks to investigate discrete reward processes One such task is the Response Bias Probabilistic Reward Task (hereafter referred to as probabilistic reward task (PRT)), a laboratory-based task designed to objectively assess reward responsiveness, that is, participants’ ability to modulate behavior as a function of reward.[5] In this task, a signal detection approach is used, whereby subjects must discriminate between two ambiguous stimuli (for example, mouths varying slightly in length on a cartoon face) displayed rapidly on a computer screen in order to receive a monetary reward. Reward responsiveness assessed in this task reflects the rapid shaping of future behavioral choices based on prior reinforcement experiences

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