Fig. 1.
Semaglutide treatment decreases alcohol intake and prevents relapse drinking in male and female rats. (A) Schematic illustration of the alcohol drinking experiment, in which semaglutide was injected acutely at three alcohol drinking sessions (S1, S4, S7). (B) In male rats, semaglutide (0.026 mg/kg, n = 12) reduces the overall alcohol intake compared to vehicle (n = 12); a reduction specifically evident at alcohol drinking session 1 and 7. (C) As further shown in males, in comparison to vehicle (n = 12) semaglutide (0.052 mg/kg, n = 12) decreases alcohol intake at each treatment session. Similarly, compared with vehicle (n = 12 in each test) both semaglutide doses, (D) 0.026 mg/kg (n = 12) and (E) 0.052 mg/kg (n = 12), reduce alcohol intake at each treatment session in female rats. (F) Schematic illustration of the alcohol drinking experiment, in which semaglutide was injected repeatedly at five subsequent alcohol drinking sessions (S1, S2, S3, S4, S5). (G) In this design, repeated semaglutide (0.026 mg/kg, n = 12) treatment reduces alcohol intake in male rats compared to vehicle (n = 12). (H) Additionally, in comparison to vehicle (n = 12), repeated semaglutide treatment (0.026 mg/kg, n = 12) lowered alcohol intake in female rats. This decline is evident at drinking session 2, 3 and 4 in males, and at each session in females. (I) Schematic illustration of the alcohol drinking experiment, in which the effect of semaglutide on relapse-like drinking after alcohol withdrawal was tested. Semaglutide is injected 60 min prior to alcohol exposure, thereafter the rats consumed alcohol for 48 h. (J) The % increase in alcohol intake from baseline (dotted line) is reduced by semaglutide. Specifically, alcohol withdrawal induces a relapse drinking (t (13) = 3.29, P = 0.0059, paired t-test, n = 14) in male rats, and semagltuide blocks the relapse-like drinking (t (14) = 2.67, P = 0.0187, paired t-test, n = 15) (data not shown). (K) Additionally, semaglutide decreases the alcohol intake 24 and 48 h after treatment. (L) In female rats, semaglutide reduces the % increase in alcohol intake from baseline (dotted line). Indetail, alcohol withdrawal trends to cause relapse-like drinking (t (14) = 1.18, P = 0.1287, paired t-test, n = 14) in female rats and this was prevented by semaglutide treatment (t (15) = 4.65, P = 0.0003, paired t-test, n = 16) (data not shown). (M) The reduced alcohol intake is also evident 24 and 48 h after semaglutide treatment. Overall interaction effect (B–E) and overall treatment effect (G–H) from two-way ANOVA with repeated measures is stated in figure. J–K data were analysed with a paired t-test and K-L wih an unpared t-test. Experiments were not replicated. Data are presented as mean ± SEM, significant data are illustrated by ∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.001. Syringe indicates time of injection.