<p class="first" id="P1">Adolescence is a period of major behavioral and brain reorganization.
As diagnoses
and treatment of disorders like attention deficit hyperactivity disorder (ADHD) often
occur during adolescence, it is important to understand how the prefrontal cortices
change and how these changes may influence the response to drugs during development.
The current study uses an adolescent rat model to study the effect of standard ADHD
treatments, atomoxetine and methylphenidate on attentional set shifting and reversal
learning. While both of these drugs act as norepinephrine reuptake inhibitors, higher
doses of atomoxetine and all doses of methylphenidate also block dopamine transporters
(DAT). Low doses of atomoxetine, were effective at remediating cognitive rigidity
found in adolescents. In contrast, methylphenidate improved performance in rats unable
to form an attentional set due to distractibility but was without effect in normal
subjects. We also assessed the effects of GBR 12909, a selective DAT inhibitor, but
found no effect of any dose on behavior. A second study in adolescent rats investigated
changes in norepinephrine transporter (NET) and dopamine beta hydroxylase (DBH) density
in five functionally distinct subregions of the prefrontal cortex: infralimbic, prelimbic,
anterior cingulate, medial and lateral orbitofrontal cortices. These regions are implicated
in impulsivity and distractibility. We found that NET, but not DBH, changed across
adolescence in a regionally selective manner. The prelimbic cortex, which is critical
to cognitive rigidity, and the lateral orbitofrontal cortex, critical to reversal
learning and some forms of response inhibition, showed higher levels of NET at early
than mid- to late adolescence.
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