The utility of rat models of impulsivity in developing pharmacotherapies for impulse control disorders

Abstract

High levels of impulsive behaviours are a clinically significant symptom in a range of psychiatric disorders, such as attention deficit hyperactivity disorder, bipolar disorder, personality disorders, pathological gambling and substance abuse. Although often measured using questionnaire assessments, levels of different types of impulsivity can also be determined using behavioural tests. Rodent analogues of these paradigms have been developed, and similar neural circuitry has been implicated in their performance in both humans and rats. In the current review, the methodology underlying the measurement of different aspects of impulsive action and choice are considered from the viewpoint of drug development, with a focus on the continuous performance task (CPT), stop-signal task (SST), go/no-go and delay-discounting paradigms. Current issues impeding translation between animal and human studies are identified, and comparisons drawn between the acute effects of dopaminergic, noradrenergic and serotonergic compounds across species. Although the field could benefit from a more systematic determination of different pharmacological agents across paradigms, there are signs of strong concordance between the animal and human data. However, the type of impulsivity measured appears to play a significant role, with the SST and delay discounting providing more consistent effects for dopaminergic drugs, while the CPT and SST show better predictive validity so far for serotonergic and noradrenergic compounds. Based on the available data, it would appear that these impulsivity models could be used more widely to identify potential pharmacotherapies for impulse control disorders. Novel targets within the glutamatergic and serotonergic system are also suggested. LINKED ARTICLESThis article is part of a themed issue on Translational Neuropharmacology. To view the other articles in this issue visit http://dx.doi. org/10.1111/bph.2011.164.issue-4 Abbreviations 5CSRT, five-choice serial reaction time task; 5-HT, serotonin; ADHD, attention deficit hyperactivity disorder; AMPA, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; BART, Balloon Analogue Risk Task; BD, bipolar disorder; BIS-11, 11-point Barratt Impulsiveness Scale; BPD, borderline personality disorder; CPT, continuous performance task; DA, dopamine; DAT, dopamine transporter; ICD, impulse control disorder; ICD-10, International Statistical Classification of Diseases and Related Health Problems, 10th Revision; IGT, Iowa Gambling Task; mGluR, metabotropic glutamate receptor; mPFC, medial prefrontal cortex; NA, noradrenaline (norepinephrine); OCD, obsessive-compulsive disorder; PAM, positive allosteric modulator; PG, pathological gambling; SSRI, serotonin selective reuptake inhibitor; SSRT, stop signal reaction time; SST, stop-signal task Impulsivity and impulse control disordersImpulsivity can be broadly defined as acting, or making decisions, without appropriate forethought, thereby enhancing the potential for negative consequences. A healthy level of impulsivity ca...

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