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. 2022 Jan 10;25(5):412–424. doi: 10.1093/ijnp/pyac004

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© The Author(s) 2022. Published by Oxford University Press on behalf of CINP.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

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Figure 4. — Function of TMEFF1 in response to cue-induced incubation of morphine craving. (A) Experimental timeline. (B) Schematics of the in vivo manipulation and a representative image of the expression of viruses in the NAcC and NAcSh. (C) The expression of TMEFF1 was decreased or increase after injection of rAAV-shRNA-TMEFF1 or rAAV-TMEFF1 by western-blot analysis. (D) Schematics of the representative images of the injection of the knockdown viruses of TMEFF1 (rAAV-TRE-U6-shTMEFF1-CMV-mCherry pA) in the NAcC (red dots) and NAcSh (black dots). (E) Downregulation of TMEFF1 in the NAcC induced the CPP scores decreased on T2 in 5 mg/kg morphine conditioned mice. ***P < .001 vs control and rAAV-vector. (F) Schematics of the representative images of the injection of overexpression viruses of TMEFF1 (rAAV- TRE-CMV-TMEFF1-mCherry-WPRE pA) in the NAcC (red dots) and NAcSh (black dots). (G) The overexpression of TMEFF1 in the NAcC induced the CPP scores increased on T2 in 1 mg/kg morphine-conditioned mice. ***P < .001 vs control, ***P < .001 vs rAAV-vector.