Chronic opioid exposure produces increased heroin self-administration in rats.
The purpose of this study was to determine the significance of chronic opioid exposure on the level of heroin self-administration in the rat. Rats were divided into morphine (M, subcutaneous morphine pellets) and placebo (P, subcutaneous placebo pellets) groups and self-administered several different doses of heroin during daily limited access 1-h sessions and prolonged access 8-h sessions. No effects on heroin self-administration occurred when the rats were implanted with morphine pellets and allowed to self-administer heroin in a limited access paradigm (1-h group). However, rats with morphine pellet implantation showed a rapid escalation (Days 0-3 post-pellet) in heroin self-administration in the more prolonged access group (8 h group) compared to placebo-pelleted animals also with 8-h access. Ultimately, placebo-pelleted 8-h exposed animals showed an escalation in heroin self-administration but this effect was delayed until Days 16-18 post-pellet. These results suggest that passive administration of morphine sufficient to produce and maintain dependence facilitates escalation in heroin intake.
Walker
John R
JR
Department of Neuropharmacology, The Scripps Research Institute, CVN-7, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Chen
Scott A
SA
Moffitt
Heather
H
Inturrisi
Charles E
CE
Koob
George F
GF
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004343:Drug Implants; D003932:Heroin / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D006556:Heroin Dependence / Q000523:psychology*; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology; D009294:Narcotics / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000523:psychology
D004343:Drug Implants; D009294:Narcotics; D003932:Heroin; D009020:Morphine