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. 2023 Aug 31;14:1180512. doi: 10.3389/fphar.2023.1180512

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Copyright © 2023 Aranäs, Blid Sköldheden and Jerlhag.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Effects of the combination of semaglutide and varenicline on alcohol intake in male and female rats (A) Timeline for the alcohol drinking experiment in which male (n = 24) and female (n = 23) rats were injected with semaglutide, varenicline or their combination in a Latin square design. Red symbols alcohol drinking session [corresponding to alcohol drinking session shown in (B–M)], and blue a water drinking day. The syringe indicates the sessions in which a drug was injected. The timeline was created with BioRender.com. Males: compared to vehicle semaglutide alone or in combination with varenicline decreases (B) alcohol intake and (C) alcohol preference, but the combination does not decline these alcohol parameters more than semaglutide alone. On other hand, neither treatment altered the (D) water and (E) total fluid intake. Further, semaglutide as monotherapy or combined with varenicline reduces (F) food intake and (G) body weight change, but with a similar magnitude. Varenicline does not affect any of the studied parameters, and in comparison to varenicline the combination reduces alcohol intake, preference for alcohol, food intake and body weight change (Figures 1B–G). Females: in comparison to vehicle, semaglutide and the combination decreases (H) alcohol intake and (I) preference for alcohol, and no additive-like effects were found. Whereas the (J) water intake is unaltered by semaglutide or varenicline treatment, their combination increases water intake. On the contrary, (K) treatment does not affect the total fluid intake. Further, with a similar magnitude both semaglutide alone or in combination reduces (L) food intake and (M) body weight change. Varenicline does not affect any of the studied parameters, and in comparison to varenicline the combination reduces alcohol intake, preference for alcohol, food intake and body weight change and increases water intake (Figures 1H–M). Data are presented as mean ± SEM, significant data are illustrated by *p < 0.05, **p < 0.01, ***p < 0.001 in comparison to vehicle. +p < 0.05, ++p < 0.01, +++p < 0.001 in comparison to varenicline. Vehicle (Veh), semaglutide (Sem), varenicline (Var), semaglutide and varenicline combination (Com).