Abstract
The purpose of this study was to examine the discrimination of agonist-antagonist opioids in humans trained in a two-choice hydromorphone/not hydromorphone discrimination. Eight adult male volunteers with histories of opioid abuse who were not currently physically dependent were trained to discriminate the mu receptor agonist hydromorphone (3 mg/70 kg, i.m.) (“Drug A”) from a “Not Drug A” training condition (saline placebo). Volunteers received financial reinforcement for correct responses. After training, generalization dose-effect curves for hydromorphone, butorphanol, pentazocine, nalbuphine, and buprenorphine were determined. Other subjective, behavioral, and physiological measures were concurrently collected in all sessions. In generalization testing hydromorphone and buprenorphine produced dose-related increases in hydromorphone-appropriate responses. Pentazocine produced an inverted U-shaped dose-response curve with complete substitution at 32 mg/70 kg but not at 64 mg/70 kg. Butorphanol and nalbuphine did not completely substitute for hydromorphone at any dose tested. These results differ from an earlier two-choice, Drug A versus Drug B (hydromorphone/saline) discrimination study. After Drug/Not Drug instructions the behavioral discriminations of agonist-antagonist opioids were more consistent with their putative agonist activities at the mu opioid receptor and with their subjective effects profiles than was the case after Drug A versus Drug B instructions. These results suggest that instructions are an important factor in the outcome of human drug discrimination studies.
Footnotes
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Send reprint requests to: Dr. Kenzie L. Preston, NIDA Intramural Research Program, 5500 Nathan Shock Dr., Baltimore, MD 21224. E-mail: kpreston{at}intra.nida.nih.gov
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↵1 The work was supported by United States Public Health Service Research Grants DA-04089 and Research Scientist Award DA-00050 from the National Institute on Drug Abuse.
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↵2 Dr. Preston is currently supported by funds from the National Institute on Drug Abuse Intramural Research Program.
- Abbreviations:
- ARCI
- Addiction Research Center Inventory
- DSST
- Digit Symbol Substitution Test
- LSD
- Lysergic Acid Diethylamide
- MBG
- Morphine-Benzedrine group
- PCAG
- Pentobarbital, Chlorpromazine, Alcohol group
- BG
- Benzedrine group
- VAS
- visual analog scale(s)
- CHO
- Chinese hamster ovary
- GTPγS
- guanosine 5′-3-O-(thio)triphosphate
- HSD
- honestly significant difference
- Received February 18, 2000.
- Accepted June 14, 2000.
- U.S. Government
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