Delta9-THC training dose as a determinant for (R)-methanandamide generalization in rats

Psychopharmacology (Berl). 1998 Dec;140(4):519-22. doi: 10.1007/s002130050797.

Abstract

The objective of this study was to examine if (R)-methanandamide, a metabolically stable chiral analog of the endogenous ligand anandamide, is a cannabimimetic with a lower efficacy than delta9-THC. Employing a two-lever choice drug discrimination procedure, rats were trained to discriminate between 1.8, 3.0, or 5.6 mg/kg delta9-tetrahydrocannabinol (delta9-THC) and vehicle. Different training doses were used in order to create assays with different efficacy demands. Generalization tests with 18 mg/kg (R)-methanandamide yielded around 90% delta9-THC responses in the two lower delta9-THC training dose conditions. However, only around 60% delta9-THC responses occurred in the 5.6 mg/kg delta9-THC training dose condition in tests with 18 mg/kg (R)-methanandamide; a higher dose (30 mg/kg) produced even fewer delta9-THC-appropriate responses in this group. Morphine did not substitute for delta9-THC. In conclusion, the data with delta9-THC and (R)-methanandamide indicate that cannabinoid agonists can have varying degrees of intrinsic activity at a receptor site, or may produce their behavioral actions through multiple mechanisms, or both.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Arachidonic Acids / administration & dosage
  • Arachidonic Acids / pharmacology*
  • Discrimination Learning / drug effects
  • Discrimination, Psychological / drug effects*
  • Dose-Response Relationship, Drug
  • Dronabinol / administration & dosage
  • Dronabinol / pharmacology*
  • Generalization, Response / drug effects*
  • Hallucinogens / administration & dosage
  • Hallucinogens / pharmacology*
  • Male
  • Morphine / pharmacology
  • Narcotics / pharmacology
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Arachidonic Acids
  • Hallucinogens
  • Narcotics
  • methanandamide
  • Morphine
  • Dronabinol