Figure 1.

Timeline of the study and test design. A. The study consisted of 3 phases. During Phase 1, rats had 5 min access to a saccharin cue followed by the opportunity to self-administer either heroin or saline 5 days a week for 15 trials. Phase 2 consisted of a 16-day period of home cage abstinence followed by Cue-induced seeking/Drug-induced Reinstatement Test 1. During this period rats were treated with a daily ip injection of either Veh (saline) or 2.4 μg/kg Exendin-4 (Ex-4). On phase 3, rats were subjected to a daily pairing of saccharin with a 6-h extinction period for 9 days followed by Drug-induced Reinstatement Test 2. B. During Cue-induced Seeking and Drug-induced Reinstatement Test 1 rats received an injection of either Veh or Ex-4. One hour later, they were given 5-min access to saccharin followed by a 5-hour period of extinction. After the 5^th hour, an infusion of either heroin or saline was automatically delivered and reinstatement of heroin seeking behavior (Drug-induced seeking) was recorded for one hour. C. During Drug-induced Reinstatement Test 2, the rats were given four hours of extinction. Then, they were injected with Veh or Ex-4 at the end of h 2, the iv heroin prime injection was infused at the end of h 3, and reinstatement of heroin seeking behavior was examined for 1 h thereafter.