Behavioral and Pharmacological Studies on the Validation of a New Animal Model for Attention Deficit Hyperactivity Disorder

Abstract

Childhood hyperactivity (attention deficit hyperactivity disorder, ADHD) is a common behavior disorder among grade-school children. The characteristic symptoms are attentional problems and hyperkinesia. A number of animal models for ADHD syndrome have been developed, but very few of these models are truly representative in that they rarely describe both hyperactivity and attentional problems. Frequently the disorder has been induced in animals by pharmacological manipulations or exogenous brain lesions which are distinct from the disturbances in normal developmental processes which ultimately lead to ADHD. The main purpose of the present research was to develop a new animal model of ADHD, such that it would include an attention deficit, hyperactivity and alleviation by treatment with a psychostimulant. We used rats trained for a 5-choice serial reaction time task which assessed sustained attention. In this behavioral paradigm, rats are required to discriminate spatially a short visual stimulus that will occur randomly in one of five locations and have to maintain an adequate activity level. The ability of a rat to maintain its attention on the task can be measured by counting choice accuracy (percent correct responses), whereas percentage of premature responses indicates the level of motoric activity. According to the present results, rats performing poorly in the task have poorer choice accuracy and they make more premature responses than well performing individuals, i.e., a clear correlation was observed between these parameters (r= −0.59,p< .001). Interestingly, choice accuracy of poorly performing rats was found to be better at the beginning of testing, but it became impaired toward the end of testing session. It was also found that the deficiency was not due to impaired visual discrimination, since a reduction in the intensity of the visual stimulus impaired to a similar extent the performance of normal and poorly performing subjects. Equally, no relationship was observed between choice accuracy and the latencies to collect earned food pellets after the correct responses, indicating that motivational factors do not underlie the attention deficit or excessive activity of poorly performers. Furthermore, methylphenidate hydrochloride at doses of 100 and 1000 μg/kg slightly improved the attentional performance of poorly performing animals. At the dose 100 μg/kg, methylphenidate slightly decreased the probability of premature responses (impulsivity) in these rats, but 1000 μg/kg methylphenidate increased the impulsivity of both normal and poorly performing rats. However, methylphenidate did not affect the choice accuracy of normal animals tested at the baseline conditions or with the reduced stimulus duration which impaired their performance. The present data indicate that rats showing poor performance when trained and tested in a 5-choice serial reaction time task may be a model for ADHD.