Attenuated responses to attention-modulating drugs in the neuroligin-3 R451C mouse model of autism.

Autor: Dingwall R; The Florey Institute of Neuroscience and Mental Health, Parkville, Melbourne, Victoria, Australia.; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria, Australia., May C; The Florey Institute of Neuroscience and Mental Health, Parkville, Melbourne, Victoria, Australia., Letschert J; The Florey Institute of Neuroscience and Mental Health, Parkville, Melbourne, Victoria, Australia., Renoir T; The Florey Institute of Neuroscience and Mental Health, Parkville, Melbourne, Victoria, Australia.; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria, Australia., Hannan AJ; The Florey Institute of Neuroscience and Mental Health, Parkville, Melbourne, Victoria, Australia.; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria, Australia., Burrows EL; The Florey Institute of Neuroscience and Mental Health, Parkville, Melbourne, Victoria, Australia.
Jazyk: angličtina
Zdroj: Journal of neurochemistry [J Neurochem] 2024 Sep; Vol. 168 (9), pp. 2285-2302. Date of Electronic Publication: 2024 Aug 02.
DOI: 10.1111/jnc.16187
Abstrakt: Attention deficits are frequently reported within the clinical autism population. Despite not being a core diagnostic feature, some aetiological theories place atypical attention at the centre of autism development. Drugs used to treat attention dysfunction are therefore increasingly prescribed to autistic patients, though currently off-label with uncertain efficacy. We utilised a rodent-translated touchscreen test of sustained attention in mice carrying an autism-associated R451C mutation in the neuroligin-3 gene (Nlgn3 R451C ). In doing so, we replicated their cautious but accurate response profile and probed it using two widely prescribed attention-modulating drugs: methylphenidate (MPH) and atomoxetine (ATO). In wild-type mice, acute administration of MPH (3 mg/kg) promoted impulsive responding at the expense of accuracy, while ATO (3 mg/kg) broadly reduced impulsive responding. These drug effects were absent in Nlgn3 R451C mice, other than a small reduction in blank touches to the screen following ATO administration. The absence of drug effects in Nlgn3 R451C mice likely arises from their altered behavioural baseline and underlying neurobiology, highlighting caveats to the use of classic attention-modulating drugs across disorders and autism subsets. It further suggests that altered dopaminergic and/or norepinephrinergic systems may drive behavioural differences in the Nlgn3 R451C mouse model of autism, supporting further targeted investigation.
(© 2024 International Society for Neurochemistry.)
Databáze: MEDLINE
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