Delta9-THC training dose as a determinant for (R)-methanandamide generalization in rats.
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.
Järbe
T U
TU
Allegheny University of the Health Sciences, Institute of Addictive Disorders, Department of Psychiatry, Philadelphia, PA 19102, USA.
Lamb
R J
RJ
Makriyannis
A
A
Lin
S
S
Goutopoulos
A
A
D000818:Animals; D001095:Arachidonic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D004193:Discrimination Learning / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000008:administration & dosage / Q000494:pharmacology*; D005794:Generalization, Response / Q000187:drug effects*; D006213:Hallucinogens / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D001095:Arachidonic Acids; D006213:Hallucinogens; D009294:Narcotics; C088155:methanandamide; D009020:Morphine; D013759:Dronabinol