Effects of cocaine hydrolase on cocaine self-administration under a PR schedule and during extended access (escalation) in rats.
OBJECTIVE
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.
Department of Psychiatry, University of Minnesota, MMC 392, Minneapolis, MN 55455, USA. mcarroll@umn.edu
Marilyn E
ME
Carroll
Yang
Y
Gao
Stephen
S
Brimijoin
Justin J
JJ
Anker
D000818:Animals; D002091:Butyrylcholinesterase / Q000737:chemistry / Q000494:pharmacology*; D003042:Cocaine / Q000008:administration & dosage* / Q000737:chemistry; D005260:Female; D006801:Humans; D051381:Rats; D017208:Rats, Wistar; D012055:Reinforcement Schedule; D012201:Reward; D012646:Self Administration
D002091:Butyrylcholinesterase; D003042:Cocaine