these neurons.105 Importantly, this genetic manipulation abolished the rewarding effects of cocaine, measured using a conditioned place preference (CPP) procedure.105 Processes independent of drug reinforcement, such as spatial learning deficits, can confound CPP. Therefore, to more rigorously investigate the involvement of striatal miRNAs in the motivational properties of cocaine we assessed intravenous cocaine self-administration in the Ago2-D2-ablated mice. Mutant animals self-administered far less cocaine than control mice across the entire cocaine dose-response curve when tested under a 1-h session on a fixed ratio 5 time-out 20 sec schedule of reinforcement use.104 Responding for food was not impacted in the mutant mice responding under the same reinforcement schedule,104 suggesting that decreased cocaine intake was not secondary to deficits in behavioral performance.
