| Title |
Atomoxetine affects transcription/translation of the NMDA receptor and the norepinephrine transporter in the rat brain – an in vivo study
|
|---|---|
| Published in |
Drug Design, Development and Therapy, December 2013
|
| DOI | 10.2147/dddt.s50448 |
| Pubmed ID | |
| Authors |
Patrick T Udvardi, Karl J Föhr, Carolin Henes, Stefan Liebau, Jens Dreyhaupt, Tobias M Boeckers, Andrea G Ludolph |
| Abstract |
Attention-deficit/hyperactivity disorder (ADHD) is the most frequently diagnosed neurodevelopmental disorder. The norepinephrine transporter (NET) inhibitor atomoxetine, the first nonstimulant drug licensed for ADHD treatment, also acts as an N-methyl-D-aspartate receptor (NMDAR) antagonist. The compound's effects on gene expression and protein levels of NET and NMDAR subunits (1, 2A, and 2B) are unknown. Therefore, adolescent Sprague Dawley rats were treated with atomoxetine (3 mg/kg, intraperitoneal injection [i.p.]) or saline (0.9%, i.p.) for 21 consecutive days on postnatal days (PND) 21-41. In humans, atomoxetine's earliest clinical therapeutic effects emerge after 2-3 weeks. Material from prefrontal cortex, striatum (STR), mesencephalon (MES), and hippocampus (HC) was analyzed either directly after treatment (PND 42) or 2 months after termination of treatment (PND 101) to assess the compound's long-term effects. In rat brains analyzed immediately after treatment, protein analysis exhibited decreased levels of the NET in HC, and NMDAR subunit 2B in both STR and HC; the transcript levels were unaltered. In rat brains probed 2 months after final atomoxetine exposure, messenger RNA analysis also revealed significantly reduced levels of genes coding for NMDAR subunits in MES and STR. NMDAR protein levels were reduced in STR and HC. Furthermore, the levels of two SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins, synaptophysin and synaptosomal-associated protein 25, were also significantly altered in both treatment groups. This in vivo study detected atomoxetine's effects beyond NET inhibition. Taken together, these data reveal that atomoxetine seems to decrease glutamatergic transmission in a brain region-specific manner. Long-term data show that the compound's impact is not due to an acute pharmacological effect but lasts or even amplifies after a drug-free period of 2 months, leading to altered development of synaptic composition. These alterations might contribute to atomoxetine's clinical effects in the treatment of ADHD, a neurodevelopmental disorder in which synaptic processes and especially a dysregulated glutamatergic metabolism seem to be involved. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Practitioners (doctors, other healthcare professionals) | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 56 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Spain | 1 | 2% |
| Switzerland | 1 | 2% |
| Unknown | 54 | 96% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 11 | 20% |
| Student > Master | 8 | 14% |
| Student > Bachelor | 8 | 14% |
| Student > Doctoral Student | 5 | 9% |
| Student > Ph. D. Student | 4 | 7% |
| Other | 9 | 16% |
| Unknown | 11 | 20% |
| Readers by discipline | Count | As % |
|---|---|---|
| Neuroscience | 12 | 21% |
| Medicine and Dentistry | 12 | 21% |
| Psychology | 9 | 16% |
| Agricultural and Biological Sciences | 3 | 5% |
| Biochemistry, Genetics and Molecular Biology | 2 | 4% |
| Other | 3 | 5% |
| Unknown | 15 | 27% |
Attention Score in Context
This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 16 June 2021.
All research outputs
#8,262,107
of 25,374,647 outputs
Outputs from Drug Design, Development and Therapy
#580
of 2,268 outputs
Outputs of similar age
#93,076
of 320,964 outputs
Outputs of similar age from Drug Design, Development and Therapy
#12
of 31 outputs
Altmetric has tracked 25,374,647 research outputs across all sources so far. This one has received more attention than most of these and is in the 66th percentile.
So far Altmetric has tracked 2,268 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.1. This one has gotten more attention than average, scoring higher than 72% of its peers.
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We're also able to compare this research output to 31 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 58% of its contemporaries.