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. 2015 Sep 16;35(37):12917–12931. doi: 10.1523/JNEUROSCI.2444-15.2015

Figure 2.

Figure 2.

KOR activation within the VTA is both necessary and sufficient for U50,488-induced CPA. a, Local inactivation of KOR by bilateral stereotaxic injection of norBNI into the VTA blocked U50,488 (5 mg/kg) induced CPA. Place preference scores for WT mice injected with either saline or 2.5 μg/μl norBNI in the VTA before U50,488 conditioning (n = 8). *p < 0.05, saline versus norBNI (t test). b, U50,488 produced significant place aversion in wild-type (KOR+/+) mice, but not in KOR−/− knock-out mice. Right, KOR−/− mice were injected with lenti-KOR, lenti-KSA, or lenti-eGFP in the VTA before U50,488 CPA. Lenti-KOR in the VTA significantly restored U50,488 CPA, whereas neither lenti-KSA nor lenti-eGFP did. Left, *p < 0.05 (t test). Right, *p < 0.05 (Bonferroni post hoc analysis after one-way ANOVA). n = 11–19. c, U50,488 (10 mg/kg) significantly reduced locomotor activity compared with saline injection in wild-type KOR+/+ mice, but not in KOR−/− or in mice receiving lenti-viral injections in VTA (n = 6–11). ***p < 0.001 (Bonferroni post hoc analysis after two-way ANOVA). x-axis labels are the same groups as in b. d, Similarly, U50,488 significantly reduced tail-withdrawal latencies compared with saline injection in wild-type KOR+/+ mice, but not in KOR−/− or in mice receiving lenti-viral injections in VTA. Withdrawal latencies were recorded before and 30 min after 15 mg/kg U50,488 (n = 11–19). ***p < 0.001 (Bonferroni post hoc after two-way ANOVA). x-axis labels are the same groups as in b. e, In contrast, latency to tail-flick was significantly increased by 15 mg/kg U50,488 in KOR−/− mice injected with lenti-KOR in DRN (n = 13). ***p < 0.001 (paired t test). f, Representative IHC images showing restoration of KOR immunoreactivity (red) in TH-ir (green) neurons of the VTA after injection of lenti-KOR or lenti-KSA into the VTA of KOR−/− mice, but not after injection of lenti-KOR into the DRN. Note the presence of double-labeled neurons (yellow) in uninjected KOR+/+ and in sections from KOR−/− mice injected with either lenti-KOR or lenti-KSA in VTA. Bottom-right inset (red rectangle), Location of the section of the parabrachial pigmented nucleus of the VTA from which images were taken (modified from Paxinos and Franklin, 2008).