The role of β-Nicotyrine in E-Cigarette abuse liability I: Drug Discrimination.

Autor:	Smethells JR; Hennepin Healthcare Research Institute, Minneapolis, MN, USA.; Department of Medicine, University of Minnesota, Minneapolis, MN, USA., S W; Hennepin Healthcare Research Institute, Minneapolis, MN, USA., P M; Hennepin Healthcare Research Institute, Minneapolis, MN, USA., Mg L; Hennepin Healthcare Research Institute, Minneapolis, MN, USA.; Department of Medicine, University of Minnesota, Minneapolis, MN, USA.; Department of Psychology, University of Minnesota, Minneapolis, MN, USA.; Department of Pharmacology, University of Minnesota, Minneapolis, MN, USA., Ap H; Hennepin Healthcare Research Institute, Minneapolis, MN, USA.; Department of Medicine, University of Minnesota, Minneapolis, MN, USA.; Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Jul 16. Date of Electronic Publication: 2024 Jul 16.
DOI:	10.1101/2024.07.12.603310
Abstrakt:	Background: β-Nicotyrine (β-Nic) is a unique minor alkaloid constituent in electronic nicotine delivery systems (ENDS) that is derived from nicotine (Nic) degradation and can reach 25% of Nic concentrations in ENDS aerosol. β-Nic slows Nic metabolism and prolongs systemic Nic exposure, which may alter the discriminability of Nic. The present study sought to examine β-Nic has interoceptive effects itself, and if it alters the subjective effects ENDS products within a drug-discrimination paradigm. Methods: The pharmacodynamics of β-Nic were examined in vitro, and a nicotine discrimination paradigm was used to determine if β-Nic (0 - 5.0 mg/kg) shares discriminative stimulus properties with Nic (0.2 mg/kg) in male (n = 13) and female (n = 14) rats after 10- & 60-min β-Nic pretreatment delays. A second group of rats was trained to discriminate β-Nic and Nornicotine (Nornic) from saline to determine if β-Nic alone has interoceptive properties and whether they are similar to Nornic. Results: β-Nic had similar binding affinity and efficacy at the α4β2 nicotinic receptor subtype as Nornic, ~50% of Nic efficacy. However, β-Nic only weakly substituted for Nic during substitution testing in female rats, but not males, whereas Nornic fully substituted for Nic. Combination testing at the 10 and 60-min pretreatment intervals showed that β-Nic dose-dependently increased the duration of nicotine's discriminative stimulus effects, especially at the 60-min delay. Drug naïve rats could reliably discriminate Nornic, but not β-Nic, from Sal. Conclusion: β-Nic increased and prolonged the interoceptive stimulus properties of Nic, suggesting it may alter to the abuse liability of ENDS through its ability to slow Nic metabolism. Competing Interests: Conflict of Interest No conflict declared.
Databáze:	MEDLINE
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