Effects of cocaine hydrolase on cocaine self-administration under a PR schedule and during extended access (escalation) in rats

Rationale and objectives: Previously, Albu-CocH, a cocaine hydrolase derived from human butyrylcholinesterase, blocked cocaine-induced reinstatement of drug seeking in rats. In the present study, rats were treated with Albu-CocH while self-administering cocaine under a progressive ratio (PR) schedule during 2-h sessions and under a fixed-ratio 1 (FR 1) schedule during 6-h sessions. Methods: In experiment 1, rats were treated with saline or Albu-CocH (2 or 4 mg/kg) before a single 2-h cocaine (0.2 mg/kg) self-administration (PR) session. In experiment 2, rats were treated with Albu-CocH or saline for the first seven of the 21-day 6-h sessions prior to cocaine (0.2 or 0.4 mg/kg) self-administration sessions (FR 1). Results: In experiment 1, Albu-CocH (vs saline) reduced cocaine infusions immediately following treatment compared with sessions pretreatment and posttreatment. In experiment 2, the Albu-CocH-treated groups (vs saline) showed an initial twofold to threefold increase in 0.2 and 0.4 mg/kg cocaine infusions over the 7 days of treatment, but they decreased to the infusion levels of saline controls by day 7. Cocaine (0.4 mg/kg) intake in the saline-treated group was elevated during the last 3 days of 6-h access compared with the first 3 days, indicating an escalation effect. Responding for 0.4 mg/kg (but not 0.2 mg/kg) cocaine during 2-h sessions after the 21 days of 6-h access was elevated in the saline groups (compared with 2-h sessions before long access) but not in the Albu-CocH-treated groups. Conclusions: Albu-CocH decreased cocaine infusions under the PR schedule, indicating a reduced reward value of cocaine (experiment 1). However, Albu-CocH, compared with saline, temporarily increased cocaine infusions during long access. The post-long access 2-h cocaine intake was not increased in the Albu-CocH-treated groups as it was in the saline-treated groups. Albu-CocH is an effective agent for reducing cocaine reward under conditions of low cocaine exposure and chronic treatment.