Enhanced cognitive flexibility and phasic striatal dopamine dynamics in a mouse model of low striatal tonic dopamine.
Journal
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
ISSN: 1740-634X
Titre abrégé: Neuropsychopharmacology
Pays: England
ID NLM: 8904907
Informations de publication
Date de publication:
02 May 2024
02 May 2024
Historique:
received:
20
02
2024
accepted:
12
04
2024
revised:
08
04
2024
medline:
3
5
2024
pubmed:
3
5
2024
entrez:
2
5
2024
Statut:
aheadofprint
Résumé
The catecholamine neuromodulators dopamine and norepinephrine are implicated in motor function, motivation, and cognition. Although roles for striatal dopamine in these aspects of behavior are well established, the specific roles for cortical catecholamines in regulating striatal dopamine dynamics and behavior are less clear. We recently showed that elevating cortical dopamine but not norepinephrine suppresses hyperactivity in dopamine transporter knockout (DAT-KO) mice, which have elevated striatal dopamine levels. In contrast, norepinephrine transporter knockout (NET-KO) mice have a phenotype distinct from DAT-KO mice, as they show elevated extracellular cortical catecholamines but reduced baseline striatal dopamine levels. Here we evaluated the consequences of altered catecholamine levels in NET-KO mice on cognitive flexibility and striatal dopamine dynamics. In a probabilistic reversal learning task, NET-KO mice showed enhanced reversal learning, which was consistent with larger phasic dopamine transients (dLight) in the dorsomedial striatum (DMS) during reward delivery and reward omission, compared to WT controls. Selective depletion of dorsal medial prefrontal cortex (mPFC) norepinephrine in WT mice did not alter performance on the reversal learning task but reduced nestlet shredding. Surprisingly, NET-KO mice did not show altered breakpoints in a progressive ratio task, suggesting intact food motivation. Collectively, these studies show novel roles of cortical catecholamines in the regulation of tonic and phasic striatal dopamine dynamics and cognitive flexibility, updating our current views on dopamine regulation and informing future therapeutic strategies to counter multiple psychiatric disorders.
Identifiants
pubmed: 38698264
doi: 10.1038/s41386-024-01868-5
pii: 10.1038/s41386-024-01868-5
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
ID : MH127377
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
ID : MH130778
Informations de copyright
© 2024. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.
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