Figure 3. Cocaine-induced locomotor stimulation and conditioned place preference in AAV-injected DAT-CI mice.

Panel A shows the locomotor activities presented as horizontal distances traveled (meters) by mice in 30 min (mean± SEM) during the first saline or cocaine conditioning session of the CPP paradigm. Wild-type mice (WT) display significant locomotor stimulation induced by 20 mg/kg cocaine compared to that after saline treatment (n = 12, P< 0.0001), whereas DAT-CI mice do not (n = 8, p > 0.05). Cocaine administration significantly stimulated locomotor activities compared to saline (n = 25, p < 0.0001) in DAT-CI mice injected with AAV- DATwt to the ventral midbrain (vMB) and striatum regions including olfactory tubercle (Tu), the nucleus accombens (Acb), and the caudate putamen (CPu). The restored locomotor stimulation by cocaine was also observed in DAT-CI mice with AAV- DATwt injected into the ventral midbrain (vMB) only (n = 13, p < 0.0001). ***, P<0.0001 in t-test comparing cocaine and saline induced locomotor activities in the same groups of mice.

Panel B shows the reward activities represented by the cocaine conditioned place preference (CPP). The CPP scores are defined as the time (in seconds) spent in the cocaine-paired environment (CS+) minus the time spent in the saline-paired environment (CS-) during the preconditioning test (Pre) and postconditioning test (Post). The wild-type mice displayed significant conditioned place-preference to 20 mg/kg cocaine – the CPP score in the post-test is significantly higher than that in the pre-test (n = 12, P<0.0001), whereas the uninjected DAT-CI mice did not (P>0.05). Injections of AAV-DATwt into the vMB and combined striatum regions of DAT-CI mice displayed significant CPP to 20mg/kg cocaine (n = 25, p < 0.001). Injections of AAV-DATwt into the vMB only also restored cocaine CPP (n = 13, P < 0.05). *, P<0.05; **, P<0.001 ***, P<0.0001 in t-tests comparing post and preconditioning CPP scores in the same group of mice.