Reinforcing and subjective effects of morphine in human opioid abusers: effect of dose and alternative reinforcer.
BACKGROUND
Although most opioid self-administration research has been conducted with laboratory animals, such research with humans is necessary to answer questions unique to human drug-taking behavior.


OBJECTIVE
We investigated the influence of morphine dose and an alternative non-drug reinforcer on choice between morphine versus money and examined the relationship between drug-reinforced behavior and subjective euphoria.


METHODS
Five male opioid users participated in the 7-week study. During the first 5 weeks, a single dose of morphine (0, 4, 8, 16, or 32 mg/70 kg) was available each week. On Monday, subjects received an IM injection of the dose tested that week. On Tuesday, Thursday, and Friday, subjects could work for morphine or money under a second-order, progressive ratio schedule. For each primary ratio completed on the drug lever, subjects earned one-ninth of the available drug dose, and for each ratio completed on the money lever, subjects earned $1. Total amount of drug earned was administered in a single IM injection at the end of the session; money earned was credited to the subject's account.


RESULTS
As morphine dose increased, responding for drug increased in an orderly manner and responding for money decreased. During the final phase of the study, the lowest and highest doses that maintained drug responding for each subject were repeated, and the value of the alternative reinforcer was increased to $2 per ratio. This manipulation was associated with decreased drug-maintained responding at the lowest, but not the highest, reinforcing dose of morphine.


CONCLUSIONS
The progressive ratio, concurrent access procedure may be useful in predicting the outcome of drug abuse treatment interventions that use alternate reinforcement strategies.
Heishman
S J
SJ
Clinical Pharmacology and Therapeutics Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224, USA. sheish@intra.nida.nih.gov
Schuh
K J
KJ
Schuster
C R
CR
Henningfield
J E
JE
Goldberg
S R
SR
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009293:Opioid-Related Disorders / Q000523:psychology*; D012054:Reinforcement, Psychology; D012119:Respiration / Q000187:drug effects
D009020:Morphine