Knock-out of the critical nitric oxide synthase regulator DDAH1 in mice impacts amphetamine sensitivity and dopamine metabolism.
Amphetamine
Behaviour
DDAH1
Dopamine
Knock-out mice
Nitric oxide
Journal
Journal of neural transmission (Vienna, Austria : 1996)
ISSN: 1435-1463
Titre abrégé: J Neural Transm (Vienna)
Pays: Austria
ID NLM: 9702341
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
received:
09
11
2022
accepted:
28
01
2023
medline:
29
8
2023
pubmed:
16
2
2023
entrez:
15
2
2023
Statut:
ppublish
Résumé
The enzyme dimethylarginine dimethylaminohydrolase 1 (DDAH1) plays a pivotal role in the regulation of nitric oxide levels by degrading the main endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA). Growing evidence highlight the potential implication of DDAH/ADMA axis in the etiopathogenesis of several neuropsychiatric and neurological disorders, yet the underlying molecular mechanisms remain elusive. In this study, we sought to investigate the role of DDAH1 in behavioral endophenotypes with neuropsychiatric relevance. To achieve this, a global DDAH1 knock-out (DDAH1-ko) mouse strain was employed. Behavioral testing and brain region-specific neurotransmitter profiling have been conducted to assess the effect of both genotype and sex. DDAH1-ko mice exhibited increased exploratory behavior toward novel objects, altered amphetamine response kinetics and decreased dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) level in the piriform cortex and striatum. Females of both genotypes showed the most robust amphetamine response. These results support the potential implication of the DDAH/ADMA pathway in central nervous system processes shaping the behavioral outcome. Yet, further experiments are required to complement the picture and define the specific brain-regions and mechanisms involved.
Identifiants
pubmed: 36792833
doi: 10.1007/s00702-023-02597-7
pii: 10.1007/s00702-023-02597-7
pmc: PMC10460711
doi:
Substances chimiques
Amidohydrolases
EC 3.5.-
Amphetamine
CK833KGX7E
Dopamine
VTD58H1Z2X
Enzyme Inhibitors
0
Nitric Oxide
31C4KY9ESH
Nitric Oxide Synthase
EC 1.14.13.39
dimethylargininase
EC 3.5.3.18
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1097-1112Informations de copyright
© 2023. The Author(s).
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