Excitation of the DRN→NAc 5-HT projection by DREADDs abolished cocaine-induced CPP and produced antidepressant-like behaviors. Gq- and blank-DREADD-expressing mice received 7.5 mg/kg cocaine, whereas Gi-DREADD-expressing mice received 4 mg/kg cocaine. (a) Timeline of AAV microinjection and behavioral tests. Effect of cocaine on CPP in Cre+ mice expressing Gq-DREADD (b), Gi-DREADD (c), and blank-DREADD (d). Effect of cocaine on CPP in Cre− mice expressing Gq-DREADD (e), Gi-DREADD (f), and blank-DREADD (g). **P<0.01, ***P<0.001, CS− of post-test vs CS+ of post-test. Effect of CNO (1 mg/kg, i.p.) injection on TST in Cre+ and Cre− mice expressing Gq-DREADD, (h) Gi-DREADD (i), and blank-DREADD (j). *P<0.05, Cre+ vs Cre−. Cre+, Fev-cre transgenic mice; Cre−, their littermates and non-cre-expressing mice.