Figure 5.

Genetically manipulating Rac1 activity in the vmPFC bidirectionally regulates drug withdrawal memory extinction and endocytosis of GABA_ARs. A–D, Knockdown of the Rac1 expression by Rac1-shRNA impaired CPA extinction and suppressed endocytosis of GABA_AR β3 subunits. A, Infection of the vmPFC with lentivirus expressing Rac1-shRNA was visualized by fluorescence microscope. B, Infection of lentivirus expressing Rac1-shRNA attenuated Rac1 expression within the vmPFC. C, Knockdown of the Rac1 expression in the vmPFC with Rac1-shRNA impaired CPA extinction. D, Knockdown of the Rac1 expression in the vmPFC with Rac1-shRNA suppressed endocytosis of GABA_AR β3 subunits. *p < 0.05, compared with control shRNA or no-extinction control groups. ^#p < 0.05, compared with control shRNA groups. E–H, Facilitation of CPA extinction and endocytosis of GABA_AR β3 subunits were observed in floxed mice to express constitutively active form of Rac1 induced by adeno-associated virus carrying Cre recombinase (AAV-Cre). E, Infection of the vmPFC with AAV-Cre was visualized by fluorescence microscope. B, Elevation of Rac1 activity was induced by expressing constitutively active Rac1 in the vmPFC through AAV-Cre. G, H, The constitutively active Rac1 mice displayed acceleration of CPA extinction and augmentation of endocytosis of GABA_AR β3 subunits. *p < 0.05, compared with AAV-GFP control groups (two-tailed Student's t test or two-way ANOVA followed by Bonferroni's post hoc test). ^#p < 0.05, compared with no-extinction control groups (two-tailed Student's t test or two-way ANOVA followed by Bonferroni's post hoc test). Error bars indicate mean ± SEM (n = 6).