The dual orexin receptor antagonist TCS1102 does not affect reinstatement of nicotine-seeking

Shaun Yon Seng Khoo, Gavan P. McNally, Kelly J. Clemens

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10 Citations (Scopus)
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The orexin/hypocretin system is important for appetitive motivation towards multiple drugs of abuse, including nicotine. Both OXand OXreceptors individually have been shown to influence nicotine self-Administration and reinstatement. Due to the increasing clinical use of dual orexin receptor antagonists in the treatment of disorders such as insomnia, we examined whether a dual orexin receptor antagonist may also be effective in reducing nicotine seeking. We tested the effect of intracerebroventricular (i.c.v.) administration of the potent and selective dual orexin receptor antagonist TCS1102 on orexin-A-induced food self-Administration, nicotine self-Administration and reinstatement of nicotine-seeking in rats. Our results show that 30 μg of TCS1102 i.c.v. abolishes orexin-A-induced increases in food self-Administration but does not reduce nicotine self-Administration. Neither i.c.v. 10 μg nor 30 μg of TCS1102 reduced compound reinstatement after short-Term (15 days) selfadministration nicotine, but 30 μg transiently reduced cue/nicotine compound reinstatement after chronic self-Administration (29 days). These results indicate that TCS1102 has no substantial effect on motivation for nicotine seeking following chronic self-Administration and no effect after shorter periods of intake. Orexin receptor antagonists may therefore have little clinical utility against nicotine addiction.

Original languageEnglish
Article number0173967
Number of pages16
JournalPLoS ONE
Issue number3
Publication statusPublished - 15 Mar 2017
Externally publishedYes

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Copyright the Author(s) 2017. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.


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