Dysfunctions in Dopamine Systems and ADHD: Evidence From Animals and Modeling
Animal models are useful for characterizing neural substrates of neuropsychiatric disorders. Several models have been proposed for the study of Attention Deficit Hyperactivity Disorder (ADHD). The models can be divided into various groups: (i) genetically derived hyperactivity/ inattention, (ii) ani...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
Hindawi Limited
2004-01-01
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| Series: | Neural Plasticity |
| Online Access: | http://dx.doi.org/10.1155/NP.2004.97 |
| Summary: | Animal models are useful for characterizing
neural substrates of neuropsychiatric disorders.
Several models have been proposed for the
study of Attention Deficit Hyperactivity Disorder
(ADHD). The models can be divided into various
groups: (i) genetically derived hyperactivity/
inattention, (ii) animal models showing symptoms
after pharmacological intervention, and (iii)
those based on spontaneous variations in a
random population. Spontaneously hypertensive
(SHR) and Naples High Excitability (NHE) rats
show behavioral traits featuring the main
aspects of ADHD in humans but show different
changes in dopamine (DA) systems. In fact, the
enzyme tyrosine hydroxylase is hyperexpressed
in NHE rats and hypoexpressed in SHR. The DA
transporter is hyperexpressed in both lines,
although in the SHR, DAT activity is low
(reduced DA uptake). The DA levels in the
striatum and prefrontal cortex are increased in
the juvenile SHR, but are decreased in handled
young and non-handled older animals. The
mRNA of the D1 DA receptor is upregulated
in the prefrontal cortex of SHR and downregulated
in NHE. The D2 DA receptors are
likely to be hypofunctioning in SHR, although
the experimental evidence is not univocal,
whereas their mRNA is hyperexpressed in
NHE. Thus, in SHR both the mesocortical and
mesolimbic DA pathways appear to be
involved, whereas in NHE only the mesocortical
system. To understand the effects of
methylphenidate, the elective ADHD drug
treatment in humans, in a dysfunctioning DA
system, we realized a simple mathematical
model of DA regulation based on experimental
data from electrophysiological, cyclic
voltammetry, and microdialysis studies. This
model allows the estimation of a higher firing
frequency of DA neurons in SHR rats and
suggests that methylphenidate increases
attentive processes by regulating the firing rate
of DA neurons. |
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| ISSN: | 2090-5904 1687-5443 |