Antisense knockdown of GLT-1 prevented the inhibition of ethanol and nicotine intake induced by intranasal administration of adipose tissue-derived MSC secretome. a A single intranasal secretome administration to chronical ethanol-drinking rats that had received a prior lateral ventricle injection of either control antisense oligo (light blue squares) or vehicle (blue triangles) induced a 65% and 75% inhibition of ethanol intake, respectively, versus chronic ethanol-drinking rats treated with vehicle both intracerebrally and intranasally (red circles). Pretreatment with an anti-GLT-1 antisense oligo (pink diamonds) fully prevented the inhibition of ethanol intake induced by intranasal secretome. One-way ANOVA: F3,12 = 93, p < 0.0001; Bonferroni post-hoc: p < 0.001, GLT-1 oligo/secretome versus control oligo/secretome and versus vehicle/secretome; p < 0.001, vehicle/vehicle versus vehicle/secretome and versus control oligo/secretome. b A single intranasal secretome administration to chronical nicotine-drinking rats that had received a prior injection of control antisense oligo (light blue square) or vehicle (blue triangle) induced a 77% and 75% inhibition of nicotine intake, respectively, versus nicotine-drinking rats treated with vehicle both intracerebrally and intranasally (red circles). Pretreatment with the anti-GLT-1 antisense oligo (pink diamond) fully prevented the inhibition of nicotine intake induced by the subsequent intranasal secretome administration; one-way ANOVA: F3,12 = 23, p < 0.0001; Bonferroni post-hoc: p < 0.001, GLT-1 oligo/secretome versus control oligo/secretome and versus vehicle/secretome; p < 0.001, vehicle/vehicle versus control oligo/secretome and versus vehicle/secretome