Dopamine D1 receptor‐expressing neurons activity is essential for locomotor and sensitizing effects of a single injection of cocaine

Dopamine D1 receptors play an important role in the effects of cocaine. Here, we investigated neurons which express these (D1-neurons) acute locomotor cocaine and sensitization observed after a second injection this drug, using previously established two-injection protocol sensitization. We inhibited D1-neurons double transgenic mice conditionally expressing inhibitory Gi-coupled designer receptor exclusively activated by drugs (Gi-DREADD) D1-neurons. Chemogenetic inhibition low dose clozapine (0.1 mg/kg) decreased cocaine-induced expression Fos striatal neurons. It diminished basal activity hyper-locomotion induced (20 mg/kg). Clozapine 0.1 mg/kg had no effect itself did not alter wild-type mice. Inhibition during first administration prevented response to 10 days later. On Day 11, stimulation Gi-DREADD blocked locomotion including sensitized mice, whereas on 12, absence inhibition, all displayed These results show that chemogenetic decreases spontaneous activity. prevents induction blocks but does reverse Our study further supports central mediating its