Abstract
RationaleAcross species, effort-related motivation can be assessed by testing behaviour under a progressive ratio (PR) schedule of reinforcement. However, to date, PR tasks for rodents have been available using traditional operant response systems only.ObjectivesTouchscreen operant response systems allow the assessment of behaviour in laboratory rodents, using tasks that share high face validity with the computerised assessments used in humans. Here, we sought to optimise a rat touchscreen variant of PR and validate it by assessing the effects of a number of manipulations known to affect PR performance in non-touchscreen paradigms.MethodsSeparate groups of male Sprague-Dawley rats were trained on PR schedules with either linear (PR4) or exponential (PREXP) schedules of reinforcement. PR performance was assessed in response to manipulations in reward outcome. Animals were tested under conditions of increased reward magnitude and following reward devaluation through a prefeeding procedure. Subsequently, the effects of systemic administration of the dopamine D2/D3 receptor antagonist raclopride and the psychostimulant d-amphetamine were examined as traditional pharmacological methods for manipulating motivation.ResultsRats reinforced under PR4 and PREXP schedules consistently showed differential patterns of response rates within sessions. Furthermore, both PR4 and PREXP schedules were sensitive to suppression by prefeeding or raclopride administration. Performance under both schedules was facilitated by increasing reward magnitude or d-amphetamine administration.ConclusionsTaken together, these findings mirror those observed in lever-based PR paradigms in rats. This study therefore demonstrates the successful validation of the rat touchscreen PR task. This will allow for the assessment of motivation in rats, within the same touchscreen apparatus used for the assessment of complex cognitive processes in this species.
Highlights
Impaired motivated behaviour represents an unmet clinical need in a number of neuropsychiatric and neurodegenerative disorders
The mean duration of the post reinforcement pause (PRP) did not differ across reinforcement schedule groups (t(22) = 1.024, p = .317; Fig. 1b)
The predicted peak response rate was significantly higher in animals reinforced under the PREXP schedule (t(22) = 3.067, p < .01; Fig. 1e)
Summary
Impaired motivated behaviour represents an unmet clinical need in a number of neuropsychiatric and neurodegenerative disorders. Such impairment, often referred to as ‘apathy’, are a common and debilitating symptom in disorders such as schizophrenia (Foussias et al 2014), major depression (Treadway and Zald 2011), Alzheimer’s disease (Landes et al 2001), Parkinson’s disease (Pedersen et al 2009) and Huntington’s’ disease (Naarding et al 2009). Standard treatment approaches for these disorders have little impact upon apathy (Fervaha et al 2015; Psychopharmacology (2018) 235:2739–2753. A key stage of developing novel treatments typically involves displaying the effectiveness of a compound in a preclinical rodent model. The ability to measure motivated behaviours in rodents is of crucial importance
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