Behavioral and pharmacological studies on the validation of a new animal model for attention deficit hyperactivity disorder. 1996

T Puumala, and S Ruotsalainen, and P Jäkälä, and E Koivisto, and P Riekkinen, and J Sirviö
A. I. Virtanen Institute, University of Kuopia, Finland.

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 micrograms/kg slightly improved the attentional performance of poorly performing animals. At the dose 100 micrograms/kg, methylphenidate slightly decreased the probability of premature responses (impulsivity) in these rats, but 1000 micrograms/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.

UI MeSH Term Description Entries
D008297 Male Males
D008774 Methylphenidate A central nervous system stimulant used most commonly in the treatment of ATTENTION DEFICIT DISORDER in children and for NARCOLEPSY. Its mechanisms appear to be similar to those of DEXTROAMPHETAMINE. The d-isomer of this drug is referred to as DEXMETHYLPHENIDATE HYDROCHLORIDE. Centedrin,Concerta,Daytrana,Equasym,Metadate,Methylin,Methylphenidate Hydrochloride,Phenidylate,Ritalin,Ritalin-SR,Ritaline,Tsentedrin,Hydrochloride, Methylphenidate,Ritalin SR
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001289 Attention Deficit Disorder with Hyperactivity A behavior disorder originating in childhood in which the essential features are signs of developmentally inappropriate inattention, impulsivity, and hyperactivity. Although most individuals have symptoms of both inattention and hyperactivity-impulsivity, one or the other pattern may be predominant. The disorder is more frequent in males than females. Onset is in childhood. Symptoms often attenuate during late adolescence although a minority experience the full complement of symptoms into mid-adulthood. (From DSM-V) ADHD,Attention Deficit Disorder,Attention Deficit Hyperactivity Disorder,Brain Dysfunction, Minimal,Hyperkinetic Syndrome,Minimal Brain Dysfunction,ADDH,Attention Deficit Disorders with Hyperactivity,Attention Deficit Hyperactivity Disorders,Attention Deficit-Hyperactivity Disorder,Attention Deficit Disorders,Attention Deficit-Hyperactivity Disorders,Deficit Disorder, Attention,Deficit Disorders, Attention,Deficit-Hyperactivity Disorder, Attention,Deficit-Hyperactivity Disorders, Attention,Disorder, Attention Deficit,Disorder, Attention Deficit-Hyperactivity,Disorders, Attention Deficit,Disorders, Attention Deficit-Hyperactivity,Dysfunction, Minimal Brain,Syndromes, Hyperkinetic
D001522 Behavior, Animal The observable response an animal makes to any situation. Autotomy Animal,Animal Behavior,Animal Behaviors
D017208 Rats, Wistar A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain. Wistar Rat,Rat, Wistar,Wistar Rats
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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