Cocaine Self-Administration

Mice underwent 14 days of 2-hour cocaine (0.75 mg/kg/12.5 μl cocaine infusion; 40 infusion maximum) self-administration sessions on an FR1 schedule of reinforcement similar to that described in freely moving mice (Heinsbroek et al., 2017). The criteria for extinction were defined in the same manner as for heroin (see above), and no mice were excluded for failure to reach criteria. Mice underwent reinstatement testing using a counterbalanced design similar to the methods described above for heroin self-administration reinstatement testing, with the exception of drug-primed reinstatement involving cocaine (5 mg/kg, i.p.) rather than heroin injections immediately before the session. A subset of cocaine self-administering mice (n = 4/15) did not undergo extinction or reinstatement testing due to initial piloting. The saline self-administering mice detailed above (see section “Heroin Self-administration”) underwent acquisition concurrently with cocaine self-administration mice and were thus included as a control for both experiments.