Effect of atomoxetine on ADHD-pain hypersensitization comorbidity in 6-OHDA lesioned mice
Pharmacol. Rep. 2023-02-14; :
DOI: 10.1007/s43440-023-00459-3
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Sifeddine W(1), Ba-M’hamed S(1), Landry M(2)(3), Bennis M(4).
Author information:
(1)Laboratory of Pharmacology, Neurobiology, Anthropobiology, and Environment,
Faculty of Sciences, Cadi Ayyad University, Avenue Prince My Abdellah, B.P.
2390, 40000, Marrakesh, Morocco.
(2)University of Bordeaux, CNRS, Institute of Neurodegenerative Diseases, UMR
5293, Bordeaux, France.
(3)University of Bordeaux, CNRS, INSERM, Bordeaux Imaging Center, UMS 3420, US
4, Bordeaux, France.
(4)Laboratory of Pharmacology, Neurobiology, Anthropobiology, and Environment,
Faculty of Sciences, Cadi Ayyad University, Avenue Prince My Abdellah, B.P.
2390, 40000, Marrakesh, Morocco. .
BACKGROUND: Methylphenidate and atomoxetine are used for the treatment of
attention-deficit/hyperactivity disorder (ADHD). Our previous studies
established the validity of the 6-hydroxydopamine (6-OHDA) mouse model of ADHD
and demonstrated hypersensitivity to pain, in line with clinical reports in ADHD
patients. Acute methylphenidate treatment reduces hyperactivity and increases
attention, but does not affect pain behaviors in this mouse model. Whereas
atomoxetine has been shown to be effective against some symptoms of ADHD,
nothing is known about its possible action on comorbid pain hypersensitivity.
The objectives of the present research are (1) to investigate the effects of
acute and chronic treatment with atomoxetine on ADHD-like symptoms and
nociceptive thresholds, and (2) to explore the catecholaminergic systems
underlying these effects.
METHODS: Sham and 6-OHDA cohorts of male mice were tested for hyperactivity
(open field), attention and impulsivity (5-choice serial reaction time task
test), and thermal (hot plate test) and mechanical (von Frey test) thresholds
after acute or repeated treatment with vehicle or atomoxetine (1, 3 or
10 mg/kg).
RESULTS: Acute administration of atomoxetine (10 mg/kg) reduced the
hyperactivity and impulsivity displayed by 6-OHDA mice, without affecting
attention or nociception. However, atomoxetine administered at 3 mg/kg/day for
7 days alleviated the ADHD-like core symptoms and attenuated the hyperalgesic
responses. Furthermore, hyperlocomotion and anti-hyperalgesic activity were
antagonized with phentolamine, propranolol, and sulpiride pre-treatments.
CONCLUSION: These findings demonstrated that when administered chronically,
atomoxetine has a significant effect on ADHD-associated pain hypersensitization,
likely mediated by both α- and β-adrenergic and D2/D3 dopaminergic receptors,
and suggest new indications for atomoxetine that will need to be confirmed by
well-designed clinical trials.
© 2023. The Author(s) under exclusive licence to Maj Institute of Pharmacology
Polish Academy of Sciences.
DOI: 10.1007/s43440-023-00459-3
PMID: 36787018