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. 2020 Feb 12;6(7):eaay1502. doi: 10.1126/sciadv.aay1502

Fig. 6. Activity of the VTA-NAc pathway is required for persistence of THC CPP in female mice carrying the FAAH SNP.

Fig. 6

(A) Experimental timeline for surgery, chemogenetic manipulation, and THC CPP. FAAHC/A mice underwent THC CPP training during adolescence, followed by injection of mCherry-tagged Cre-dependent AAV expressing the inhibitory DREADD hM4Di (AAV2-hSyn-DIO-hM4Di-Gi-mCherry) into bilateral VTA and a retrograde CAV2 expressing Cre recombinase into bilateral NAc. Control mice either underwent sham surgery without viral infusions or did not receive surgery. All mice were tested in THC CPP in adulthood following a CNO injection. (B) Representative image of injection site in VTA with mCherry-tagged virus-labeled cells. (C) Control FAAHC/A mice that received CNO demonstrated increased preference for the THC-paired side, as demonstrated by a significantly increased preference score on adult test day compared to baseline day (paired t test, t8 = 3.147, *P = 0.0137, n = 9). FAAHC/A mice injected with hM4Di DREADD demonstrated no THC preference, as shown by a similar preference score on adult test day compared to baseline (paired t test, t7 = 0.3208, P = 0.7577, n = 8). (D) FAAHC/A mice injected with hM4Di DREADD that received CNO demonstrated a significantly lower difference score than control FAAHC/A mice that received CNO (unpaired t test, t15 = 2.189, *P < 0.05, n = 9 CNO control and n = 8 hM4Di DREADD).