Involvement of Norepinephrine in the Control of Activity and Attentive Processes in Animal Models of Attention Deficit Hyperactivity Disorder
Functional and morphological studies in children affected by Attention Deficit Hyperactivity Disorder (ADHD) suggest a prefrontal cortex (PFc) dysfunction. This cortical region is regulated by subcortical systems including noradrenergic (NEergic), dopaminergic (DAergic), cholinergic, serotonergic, a...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Hindawi Limited
2004-01-01
|
| Series: | Neural Plasticity |
| Online Access: | http://dx.doi.org/10.1155/NP.2004.133 |
| Summary: | Functional and morphological studies in
children affected by Attention Deficit Hyperactivity
Disorder (ADHD) suggest a prefrontal
cortex (PFc) dysfunction. This cortical region is
regulated by subcortical systems including noradrenergic
(NEergic), dopaminergic (DAergic),
cholinergic, serotonergic, and histaminergic pathways.
A wealth of data in humans and in animal
models demonstrates altered dopamine (DA)
regulation. Drugs that modulate norepinephrine
(NE) transmission are also effective in ADHD
patients, thus leading to the hypothesis of a
NEergic disorder. This review covers the
regulation of PFc functions by NE and the
interaction between the NE and DA systems, as
suggested by pharmacological, electrophysiological,
morphological, and gene knock out (KO)
studies. A negative feedback between NE and DA
neurons emerges from KO studies because KO
mice showing increased (NE transporter (NET)
KO) or decreased (DBH and VMAT2 KO) NE
levels are respectively associated with lower and
higher DA levels. Locomotor activity can be
generally predicted by the DA level, whereas
sensitivity to amphetamines is by NE/DA balance.
Some animal models of ADHD, such as
spontaneously hypertensive rats (SHR), show
alterations in the PFc and in the DA system.
Evidence about a correlation between the NE
system and hyper-locomotion activity in such
animals has not yet been clarified. Therefore, this
review also includes recent evidence on the
behavioral effects of two NET blockers,
reboxetine and atomoxetine, in two animal models
of ADHD: SHR and Naples High Excitability rats.
As these drugs modulate the DA level in the PFc,
certain effects are likely to be due to a rebalanced
DA system. We discuss the significance of the
results for theories of ADHD and make
suggestions for future experimentation. |
|---|---|
| ISSN: | 2090-5904 1687-5443 |