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Psychopharmacology
ISSN: 0033-3158 (printed version)
ISSN: 1432-2072 (electronic version)
Table of Contents
Abstract
Volume 140 Issue 4 (1998) pp 519-522
original investigation: <Delta>9-THC training dose as a determinant for (R)-methanandamide generalization in rats
T. U. C. Järbe (1), R. J. Lamb (1), A. Makriyannis (2), S. Lin (2), A. Goutopoulos (2)
(1) Allegheny University of the Health Sciences, Institute of Addictive Disorders, Department of Psychiatry, Division of Addiction Research & Treatment, Mail Stop 984, Broad and Vine Streets, Philadelphia, PA 19102, USA
(2) University of Connecticut, Departments of Pharmaceutical Sciences and Molecular Cell Biology, U-92, Storrs, CT 06269, USA
Received: 9 May 1998 / Final version: 28 May 1998
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 <Delta>9-THC. Employing a two-lever choice drug discrimination procedure, rats were trained to discriminate between 1.8, 3.0, or 5.6 mg/kg <Delta>9-tetrahydrocannabinol (<Delta>9-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% <Delta>9-THC responses in the two lower <Delta>9-THC training dose conditions. However, only around 60% <Delta>9-THC responses occurred in the 5.6 mg/kg <Delta>9-THC training dose condition in tests with 18 mg/kg
(R)-methanandamide; a higher dose (30 mg/kg) produced even fewer <Delta>9-THC-appropriate responses in this group. Morphine did not substitute for <Delta>9-THC. In conclusion, the data with <Delta>9-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
Key words <Delta>9-THC · Cannabinoids · (R)-methanandamide · Anandamides · Efficacy · Drug discrimination · Rat
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Online publication: December 9, 1998
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