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. 2022 Feb 25;43(9):2276–2288. doi: 10.1038/s41401-022-00866-x

Fig. 6. Optical activation of the VTA-NAcore DA projection pathway selectively reinstates extinguished cocaine-seeking behavior.

Fig. 6

a Representative images illustrating ChR2-mCherry expression in the VTA, NAc and mPFC in DAT-Cre mice after intra-VTA AAV-ChR2 microinjection. 10×, scale bar = 2000 μm; 20×, scale bar = 200 μm. b Schematic schedule of experiments: after the extinction of cocaine self-administration (SA), a laser was used to activate DA projections to induce cocaine relapse. c Mean numbers of nose pokes in active and inactive holes during the last 3 sessions of SA, the last 3 sessions of extinction, and the laser-induced reinstatement test. The activation of VTA-NAcore DA projections (20-Hz, 100 laser pulses) reinstated active-poke responses in mice after the extinction of SA. One-way RM ANOVA on ranks revealed a laser priming main effect: P = 0.039. Post hoc Tukey’s test revealed that activation of VTA-NAcore DA projections resulted in a difference in reinstated active-poke responses that was statistically significant (*P < 0.05, compared to the mean of last 3 sessions of extinction, n = 9). Inactive pokes were not affected by laser priming after the extinction of SA. One-way RM ANOVA revealed a treatment main effect: F(1,8) = 0.151, P = 0.708. d Activation of DA projections to the NAshell did not reinstate active-poke responses in mice after the extinction of SA. One-way RM ANOVA revealed a laser priming main effect: F(3,18) = 1.239, P = 0.325, n = 7. e Activation of DA projections to the IL did not reinstate active-poke responses in mice after the extinction of SA. One-way RM ANOVA revealed a laser priming main effect: F(3,18) = 0.696, P = 0.566, n = 7. f Activation of DA projections to the PL did not reinstate active-poke responses in mice after the extinction of SA. One-way RM ANOVA revealed a laser priming main effect: F(3,21) = 0.621, P = 0.609, n = 8.