Selective orexin 1 receptor antagonism does not affect effort-based responding for sucrose reward in rats

In rodents, orexin neuropeptides regulate motivation and reward-seeking via orexin 1 receptor (OX1R) signaling in the mesolimbic dopaminergic system. This role is clearly established for rewards inherent to drugs of abuse but less so for natural rewards. Reported effects of the selective OX1R antago...

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Bibliographic Details
Published inJournal of psychopharmacology (Oxford) Vol. 38; no. 3; p. 305
Main Authors Bergamini, Giorgio, Durkin, Sean, Steiner, Michel Alexander
Format Journal Article
LanguageEnglish
Published United States 01.03.2024
Subjects
Animals
Benzoxazoles
Conditioning, Operant
Humans
Naphthyridines
Orexin Receptors
Orexins - pharmacology
Rats
Reward
Sucrose - pharmacology
Urea - analogs & derivatives
operant testing
selective orexin 1 receptor antagonist
motivation
rats
progressive ratio test
Orexin
binge eating
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Summary:In rodents, orexin neuropeptides regulate motivation and reward-seeking via orexin 1 receptor (OX1R) signaling in the mesolimbic dopaminergic system. This role is clearly established for rewards inherent to drugs of abuse but less so for natural rewards. Reported effects of the selective OX1R antagonist (SO1RA) SB-334867 on motivation for palatable food are ambiguous. In our experimental conditions neither SB-334867, nor two additional, structurally different SO1RAs, ACT-335827 and the clinical development candidate nivasorexant, affected effort-based responding for sucrose in rats. The positive control lisdexamfetamine, approved for psychiatric disorders associated with altered reward sensitivity such as binge eating disorder, increased effort-based responding.
ISSN:1461-7285
DOI:10.1177/02698811241229523