Abstract:
:Substantial development in the pharmacological treatment for attention-deficit hyperactivity disorder (ADHD) has been made recently including approval of new non-stimulant agents targeting noradrenergic, histaminergic and dopaminergic systems. Among such, atomoxetine has been widely used, although its mechanism of action is poorly understood. It is known that central nervous system histamine is closely associated with cognition and it was recently shown that both atomoxetine and methylphenidate enhance cortical histamine release in rats. To that end, the aim of our study was to investigate the effect of atomoxetine (2 mg/kg, intraperitoneally) on histamine release using the microdialysis technique in the spontaneously hypertensive rat (SHR), a suitable genetic model for ADHD. Our data confirmed that atomoxetine increases extracellular levels of histamine in the prefrontal cortex, a brain region that is implicated in the pathophysiology of ADHD. Given the tie between histamine neurotransmission and treatment of cognitive dysfunction, we also assessed the effects of atomoxetine on learning and memory as measured by the Morris water maze in SHR. The results indicated that atomoxetine significantly ameliorated performance in the Morris water maze, consistent with its histamine-enhancing profile. In conclusion, the current study provides further support for the notion that the therapeutic effect of atomoxetine could involve activation of histamine neurotransmission within the prefrontal cortex.
journal_name
Basic Clin Pharmacol Toxicoljournal_title
Basic & clinical pharmacology & toxicologyauthors
Liu LL,Yang J,Lei GF,Wang GJ,Wang YW,Sun RPdoi
10.1111/j.1742-7843.2008.00230.xsubject
Has Abstractpub_date
2008-06-01 00:00:00pages
527-32issue
6eissn
1742-7835issn
1742-7843pii
PTO230journal_volume
102pub_type
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