Cocaine and Alcohol Self-Administration

Rats assigned to receive access to alcohol after cocaine sessions were first provided intermittent access to unsweetened alcohol (20% v/v) on alternating days for five 24-h sessions prior to surgery (see [33, 35], Supplemental Methods). Rats were trained to self-administer cocaine (or receive yoked-saline infusions) in a two-lever operant chamber (Med Associates, St. Albans, VT), whereby one press on the active lever resulted in cocaine and cue-presentation (2900 Hz tone and stimulus light). Immediately following each 2-h self-administration session, rats received 6-h access to water alone or both water and unsweetened alcohol (20% v/v) in the homecage. Self-administration continued for 10 (Experiment 1) or 12 days (Experiments 2–4), after which rats experienced daily 2-h extinction training, during which presses on the previously active lever did not yield drug or cues. No alcohol was available during this time. After a minimum of 12 extinction sessions, rats were killed for western blotting (Experiment 1) or underwent reinstatement testing (Experiments 2–4).