Figure 4. Varenicline pretreatment blunts nicotine-evoked DA signaling in the dorsal striatum.
(A) Schematic and representative image showing GRAB-DA and fiber placement in the dorsal striatum. Scale bar, 200 μm. (B) Mean ΔF/F (3 min bins) of GRAB-DA signals of mice given a subcutaneous (SC) injection of varenicline (1.5 mg/kg) or saline (0.9%). Saline was injected IP immediately after SC injections to control for the extra handling in subsequent co-injection experiments (n=12/group, two-way repeated measures ANOVA). (C) Average ΔF/F of GRAB-DA signals of mice treated with SC varenicline or saline and co-injected with IP nicotine (1.5 mg/kg). Signals are aligned to the IP injection. Blue, varenicline; grey, saline. Green on timeline represents duration of fiber photometry recording. (D) Mean ΔF/F (3-min bins) of GRAB-DA signals shown in (C) (n=14/group, two-way repeated measures ANOVA). (E) Average ΔF/F of GRAB-DA signals of mice injected with IP nicotine 30 min after a pretreatment with SC varenicline or saline. (F) Mean ΔF/F (3-min bins) of GRAB-DA signals shown in (E) (n=12/group, two-way repeated measures ANOVA, main effect of group: p<0.01). Dark lines represent means and lighter, shaded areas represent SEM. post-hoc comparisons: *p<0.05, **p<0.01, ***p<0.001. ANOVA main effect of group: ☼☼p<0.01. See Table S1 for details on statistical analyses.