Abstract

BackgroundADHD is currently defined as a cognitive/behavioral developmental disorder where all clinical criteria are behavioral. Overactivity, impulsiveness, and inattentiveness are presently regarded as the main clinical symptoms. There is no biological marker, but there is considerable evidence to suggest that ADHD behavior is associated with poor dopaminergic and noradrenergic modulation of neuronal circuits that involve the frontal lobes. The best validated animal model of ADHD, the Spontaneously Hypertensive Rat (SHR), shows pronounced overactivity, impulsiveness, and deficient sustained attention. While dopamine release is decreased in SHR, norepinephrine concentrations are elevated. The primary objective of the present research was to test effects of a range of doses of the catecholamine agonists d- and l-amphetamine on ADHD-like symptoms in SHR.MethodsThe present study tested behavioral effects of 0.64 to 1.91 mg/kg d-amphetamine; and 1.27 to 3.81 mg/kg l-amphetamine base/kg i.p. in male SHRs and their controls, the Wistar Kyoto rat (WKY). ADHD-like behavior was tested with a visual discrimination task measuring overactivity, impulsiveness and inattentiveness.ResultsThe striking impulsiveness, overactivity, and poorer sustained attention during baseline conditions in the SHR were improved by treatment with the amphetamine isomers. The dose-response curves were, however, different for the different behaviors. Most significantly, d-amphetamine reduced overactivity and impulsiveness more efficiently than comparable doses of l-amphetamine. The lowest dose of d-amphetamine and low-to-medium doses of l-amphetamine improved sustained attention. The highest dose of d-amphetamine used interfered with SHR behavior. A second study showed that the impaired sustained attention (percent correct lever choice) in the SHR was not due to impaired visual functions or poorer working memory.DiscussionThe present results indicate that overactivity and impulsiveness may to some extent be associated with imbalances in neural circuits that differ from those causing poor sustained attention and that the two amphetamine isomers may affect the different neuromodulators differently. While d-amphetamine improved SHR overactivity, impulsiveness as well as sustained attention, the behavioral effects of l-amphetamine were relatively more specific for improving sustained attention than for the other 2 symptoms. Thus, while d- and l-amphetamine affect similar neuronal systems their relative potencies may be different.

Highlights

  • Attention-deficit/hyperactivity disorder (ADHD) is currently defined as a cognitive/behavioral developmental disorder where all clinical criteria are behavioral

  • General Compared to Wistar Kyoto rat (WKY) controls, Spontaneously Hypertensive Rat (SHR) showed pronounced overactivity, impulsiveness and poorer sustained attention

  • The results showed clearer dose-response curves in the SHR than in the WKY strain. d-Amphetamine was more than twice as potent as l-amphetamine in reducing SHR hyperactivity and impulsivity

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Summary

Introduction

ADHD is currently defined as a cognitive/behavioral developmental disorder where all clinical criteria are behavioral. There is no biological marker, but there is considerable evidence to suggest that ADHD behavior is associated with poor dopaminergic and noradrenergic modulation of neuronal circuits that involve the frontal lobes. The primary objective of the present research was to test effects of a range of doses of the catecholamine agonists d- and l-amphetamine on ADHD-like symptoms in SHR. Attention-deficit/hyperactivity disorder (ADHD) is currently defined as a cognitive developmental disorder where all clinical criteria are behavioral [1]. ADHD symptoms are associated with reduced post-synaptic efficacy of dopaminergic and noradrenergic modulation of neuronal circuits that involve the frontal lobes [8,9]. It is not surprising that amphetamines and other catecholamine agonists have been the drugs of choice in medication of ADHD [8,9,12,13,14]

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