Behavioral models of impulsivity in relation to ADHD: Translation between clinical and preclinical studies

Abstract

Impulsivity, broadly defined as action without foresight, is a component of numerous psychiatric illnesses including attention deficit/hyperactivity disorder (ADHD), mania and substance abuse. In order to investigate the mechanisms underpinning impulsive behavior, the nature of impulsivity itself needs to be defined in operational terms that can be used as the basis for empirical investigation. Due to the range of behaviors that the term impulsivity describes, it has been suggested that impulsivity is not a unitary construct, but encompasses a variety of related phenomena that may differ in their biological basis. Through fractionating impulsivity into these component parts, it has proved possible to devise different behavioral paradigms to measure various aspects of impulsivity in both humans and laboratory animals. This review describes and evaluates some of the current behavioral models of impulsivity developed for use with rodents based on human neuropsychological tests, focusing on the five-choice serial reaction time task, the stop-signal reaction time task and delay-discounting paradigms. Furthermore, the contributions made by preclinical studies using such methodology to improve our understanding of the neural and neurochemical basis of impulsivity and ADHD are discussed, with particular reference to the involvement of both the serotonergic and dopaminergic systems, and frontostriatal circuitry.

Disparate cocaine-induced locomotion as a predictor of choice behavior in rats trained in a delay-discounting task

“…Notably, the lack of overlap between the novelty and cocaine response phenotypes has been described previously in male SpragueDawley rats (Gulley et al, 2003;Gulley, 2007), and suggests the LCR/HCR classification is somewhat distinct from one based on novelty and may be mediated by different neural mechanisms. It is also noteworthy that different methods of assessing impulsive behavior in rats (e.g., delay-discounting compared to DRL tasks) are likely to be focusing on particular aspects of impulsivity, and the neural mechanisms of impulsive behavior are not likely to be identical (Evenden, 1999;Winstanley et al, 2006a).…”

“…Impulsivity is a complex, multifaceted trait that is broadly defined by a lack of behavioral inhibition, which includes premature and poorly controlled actions, and impulsive choice, where decisions are poorly conceived and sensitive to delayed rewards (see Evenden, 1999;Winstanley et al, 2006a for more detailed accounts). Individuals who abuse drugs tend to exhibit heightened levels of these traits, particularly with regards to impulsive decision-making (Bornovalova et al, 2005;Coffey et al, 2003;Heil et al, 2006;Kirby and Petry, 2004;Lejuez et al, 2007;Moeller et al, 2002;Verdejo-Garcia et al, 2007).…”

Opposing Roles for 5-HT2A and 5-HT2C Receptors in the Nucleus Accumbens on Inhibitory Response Control in the 5-Choice Serial Reaction Time Task

“…There is considerable evidence implicating DA-ergic mechanisms in inhibitory response control (Cole and Robbins, 1989;Robbins, 2002;Winstanley et al, 2006;Pezze et al, 2007;Dalley et al, 2007). Neurochemical and behavioral studies indicate that 5-HT 2 receptor subtypes differentially modulate DA as well as noradrenaline function within the NAc (Gobert and Millan, 1999;Di Matteo et al, 2001;Porras et al, 2002;Bubar and Cunningham, 2006).…”

“…Clinical and preclinical research suggests that dysregulation within serotonergic (5-HT) systems is involved in impulsive behavior. Furthermore, 5-HT projections to medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) and indirect actions via 5-HT-receptors regulating PFC projections to the ventral tegmental area (VTA), are thought to be involved in attentional function and executive processes including inhibitory response control (Robbins, 2000;Chudasama and Robbins, 2004;Winstanley et al, 2006). However, the 5-HT system is complex, with at least 15 subtypes of receptor expressed in mammalian systems (for detailed review see Barnes and Sharp, 1999;Hoyer et al, 2002).…”

“…The relationship between 5-HT function and behavioral inhibition has been studied using a number of different animal models combined with manipulations of the 5-HT system (Soubrié, 1986;Robbins, 2002;Chudasama and Robbins, 2004;Winstanley et al, 2006). Depletion of forebrain 5-HT induces impulsive responding in rats when assessed using go/no-go or DRL paradigms (Fletcher, 1995;Harrison et al, 1999).…”