TY - JOUR
T1 - Low attentive and high impulsive rats: A translational animal model of ADHD and disorders of attention and impulse control
AU - Hayward, Andrew
AU - Tomlinson, A
AU - Neill, JC
N1 - AH is a PhD student part-funded by the University of Manchester (UoM) Pharmacy School and b-neuro at the UoM. JCN is a full-time employee of the UoM.
PY - 2016/2
Y1 - 2016/2
N2 - Many human conditions such as attention deficit hyperactivity disorder (ADHD), schizophrenia and drug abuse are characterised by deficits in attention and impulse control. Carefully validated animal models are required to enhance our understanding of the pathophysiology of these disorders, enabling development of improved pharmacotherapy. Recent models have attempted to recreate the psychopathology of these conditions using chemical lesions or genetic manipulations. In a diverse population, where the aetiology is not fully understood and is multifactorial, these methods are restricted in their ability to identify novel targets for drug discovery. Two tasks of visual attention and impulsive action typically used in rodents and based on the human continuous performance task (CPT) include, the well-established 5 choice serial reaction time task (5C-SRTT) and the more recently validated, 5 choice continuous performance task (5C-CPT) which provides enhanced translational value. We suggest that separating animals by behavioural performance into high and low attentive and impulsivity cohorts using established parameters in these tasks offers a model with enhanced translational value. In this review, methods to separate animals are compared and the results discussed to highlight advantages over more constrained models, in addition to potential future directions for enhanced validation. Advantages include reliability, flexibility and enhanced translation to clinical conditions, all important considerations in modelling ADHD, schizophrenia and drug abuse, conditions with multifactorial aetiology. Based on the existing evidence, we suggest that future studies should incorporate an element of behavioural separation when studying the constructs of visual attention and impulsive action of relevance to human disorders.
AB - Many human conditions such as attention deficit hyperactivity disorder (ADHD), schizophrenia and drug abuse are characterised by deficits in attention and impulse control. Carefully validated animal models are required to enhance our understanding of the pathophysiology of these disorders, enabling development of improved pharmacotherapy. Recent models have attempted to recreate the psychopathology of these conditions using chemical lesions or genetic manipulations. In a diverse population, where the aetiology is not fully understood and is multifactorial, these methods are restricted in their ability to identify novel targets for drug discovery. Two tasks of visual attention and impulsive action typically used in rodents and based on the human continuous performance task (CPT) include, the well-established 5 choice serial reaction time task (5C-SRTT) and the more recently validated, 5 choice continuous performance task (5C-CPT) which provides enhanced translational value. We suggest that separating animals by behavioural performance into high and low attentive and impulsivity cohorts using established parameters in these tasks offers a model with enhanced translational value. In this review, methods to separate animals are compared and the results discussed to highlight advantages over more constrained models, in addition to potential future directions for enhanced validation. Advantages include reliability, flexibility and enhanced translation to clinical conditions, all important considerations in modelling ADHD, schizophrenia and drug abuse, conditions with multifactorial aetiology. Based on the existing evidence, we suggest that future studies should incorporate an element of behavioural separation when studying the constructs of visual attention and impulsive action of relevance to human disorders.
KW - Animal model; ADHD; 5C-SRTT; 5C-CPT; High Performance; Low Performance
U2 - 10.1016/j.pharmthera.2015.11.010
DO - 10.1016/j.pharmthera.2015.11.010
M3 - Article
SN - 0163-7258
VL - 158
SP - 41
EP - 51
JO - Pharmacology & therapeutics
JF - Pharmacology & therapeutics
ER -