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. 2024 Nov 15;134(22):e183354.
doi: 10.1172/JCI183354.

Xylazine induces dopamine release and augments the effects of fentanyl

Joseph R Trinko  1 , Ethan Foscue  1 , Edward M Kong  1 , Aakash Basu  1   2 , Anouk M Corstens  1 , Summer L Thompson  1 , Alfred P Kaye  1   2   3   4 , Jane R Taylor  1   2   4 , Ralph J DiLeone  1   2   4
Affiliations

Xylazine induces dopamine release and augments the effects of fentanyl

Joseph R Trinko et al. J Clin Invest. .
No abstract available

Keywords: Addiction; Neuroscience.

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Conflict of interest statement

Conflict of interest: The authors have declared that no conflict of interest exists.

Figures

Figure 1
Figure 1. Xylazine induces dopamine release through an α2 adrenergic receptor effect and potentiates the neurochemical effects of fentanyl.
(A) Xylazine (red arrow) significantly induced dopamine release (n = 6/group; repeated measures [RM] 1-way ANOVA main effect of time F(44,220) = 4.499, ****P < 0.0001) and (B) reduced locomotor activity (n = 6/group; RM 1-way ANOVA main effect of time F(44,220) = 3.452, ****P < 0.0001). (C) Pretreatment with the α2 adrenergic receptor antagonist atipamezole (red arrow) significantly blocked the effects of xylazine (blue arrow) on dopamine release (n = 6/group; 2-way RM-ANOVA main effect of treatment F(1, 10) = 21.79, ***P = 0.0009; treatment × time interaction F(34, 340) = 12.19, ****P < 0.0001 analyzing 70 minutes after atipamezole and xylazine treatments). (D) Atipamezole partially attenuated the effects on locomotor activity (n = 6/group; 2-way RM-ANOVA main effect of treatment F(1,10) = 18.60, **P = 0.0015; treatment × time interaction F(34,340) = 1.872, **P = 0.0030). (E) Fentanyl treatment (red arrow) induced significant dopamine release (n = 6/group; 1-way RM-ANOVA main effect of time F(44, 220) = 34.52, ****P < 0.0001) and locomotor activity (n = 6/group; RM 1-way ANOVA main effect of time F(44,220) = 1.828, **P = 0.0026) (F). (G) Coadministration of fentanyl and xylazine (red arrow) significantly augmented the effects of fentanyl alone on dopamine release (n = 6/group;2-way RM-ANOVA main effect of treatment F(1,10) = 14.01, **P = 0.0038, and a significant interaction of treatment × time F(44, 440) = 9.751, ****P < 0.0001), while locomotor activity was reduced compared to fentanyl alone (n = 4 combo, n = 6 fentanyl; 2-way RM-ANOVA main effect of treatment F(1,8) = 60.65, ****P < 0.0001; treatment × time interaction F(44,352) = 2.343, ****P < 0.0001) (H). All error bars are SEM.
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References

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