Agonist and antagonist effects of prototype opiate drugs in fentanyl dose-dose discrimination

Psychopharmacology (Berl). 1986;90(2):222-8. doi: 10.1007/BF00181246.

Abstract

The experiments characterized the effects of fentanyl, morphine, naloxone, cyclazocine, nalorphine, ketocyclazocine and N-allylnormetazocine in rats that were trained to discriminate 0.04 mg/kg from 0.02 mg/kg fentanyl (dose-dose discrimination). The data are compared to results obtained previously in rats discriminating 0.04 mg/kg fentanyl from saline (drug-saline discrimination). In the dose-dose discrimination fentanyl and morphine produced responding appropriate to 0.04 mg/kg fentanyl at doses which were 3.0- and 1.6-fold higher, respectively, than in drug-saline discrimination. Naloxone antagonized the stimulus effects of 0.04 mg/kg fentanyl at 9.8-fold lower doses than in drug-saline discrimination. The dose-effect curves of fentanyl and naloxone in rats discriminating 0.04 mg/kg from 0.02 mg/kg fentanyl, were steeper than in rats discriminating 0.04 mg/kg fentanyl from saline. While cyclazocine, nalorphine and N-allylnormetazocine acted as mixed and partial agonists/antagonists in drug-saline discrimination, those compounds acted as pure and complete antagonists of 0.04 mg/kg fentanyl in dose-dose discrimination. The rank order of compounds in antagonizing the stimulus effects of 0.04 mg/kg fentanyl in dose-dose discrimination was naloxone greater than N-allylnormetazocine greater than cyclazocine greater than nalorphine. It is suggested that a greater magnitude of opiate activity is required for producing generalization with the same 0.04 mg/kg dose of fentanyl in dose-dose as compared with drug-saline discrimination. Dose-dose discrimination may afford a more accurate method of the discriminative stimulus properties of drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Discrimination Learning / drug effects
  • Discrimination, Psychological / drug effects*
  • Dose-Response Relationship, Drug
  • Fentanyl / antagonists & inhibitors
  • Fentanyl / pharmacology*
  • Generalization, Stimulus / drug effects
  • Male
  • Morphine / pharmacology
  • Naloxone / pharmacology
  • Narcotics / pharmacology*
  • Rats
  • Rats, Inbred Strains

Substances

  • Narcotics
  • Naloxone
  • Morphine
  • Fentanyl