Fig. 3.

In male mice, semaglutide attenuates the alcohol-induced locomotor stimulation and dopamine release in nucleus accumbens shell as well as decreases the consumption of rewarding foods. (A) Compared to vehicle (n = 12), alcohol (n = 18) causes a locomotor stimulation, and acute administration of semaglutide (0.026 mg/kg, n = 15) blocks the alcohol-induced locomotor stimulation in male mice. Additionally, semaglutide (n = 12) does not affect the activity of mice per se. (data analysed with one-way ANOVA) (B) In comparison to vehicle (n = 12), alcohol (n = 11) enhances the dopamine levels in nucleus accumbens shell of male mice. Semaglutide (n = 8) attenuates the ability of alcohol to increase dopamine in male mice, while it (n = 9) alone does not alter the dopamine levels. Data analysed with a two-way ANOVA with repeated measures. Together these findings indicate that semaglutide supresses the reward-like behaviours associated with alcohol of male mice. In further support for semaglutide's ability to suppress reward, it reduces the 4-h intake of (C) peanut butter (n = 12 per group) and (D) Nutella (n = 8 per group) in male mice. Data analysed with unpaired t-test. These findings have led to the hypothesis that semaglutide acts within the nucleus accumbens shell. (E) Illustration of the selected part of nucleus accumbens shell where the fluorescently labeled semaglutide (CY3-semaglutide) is detected. After systemic administration, CY3-semaglutide is detected in nucleus accumbens shell of alcohol drinking (F) male and (G) female rats. (H) This signal not found in alcohol drinking rats injected with vehicle. Experiments were not replicated. Data are presented as mean ± SEM, significant data are illustrated by ∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.001. +P < 0.05, ++P < 0.001 when comparing vehicle-alcohol versus semaglutide-alcohol in the microdialysis experiment.