Abstract:
:The present study estimated the apparent intrinsic activity of the cannabinoid CB1 receptor ligands CP 55,940, Delta9-tetrahydrocannabinol (Delta9-THC) and SR 141716A in a highly sensitive in vivo assay. Rats were trained to discriminate the cannabinoid CB1 receptor agonist CP 55,940 (either 0.03 or 0.014 mg/kg, i.p., t=30 min) from vehicle, in a two-lever food-reinforced procedure, and were subsequently tested with the three compounds. Although reduction of the training dose did not affect the maximum level of generalization or antagonism (>80% generalization for CP 55,940 and Delta9-THC; 0% generalization and >80% antagonism for SR 141716A), the potency of the compounds was differentially affected. Thus, the generalization curves obtained with CP 55,940 and Delta9-THC were shifted three- and sixfold to the left; whereas no potency difference was obtained for the antagonism of CP 55,940 by SR 141716A. The data are consistent with the hypothesis that the level of intrinsic activity of CP 55,940 is higher than that of Delta9-THC, and that SR 141716A may have a very low level of intrinsic activity. It is concluded that variation of the training dose increases the sensitivity of the in vivo intrinsic activity estimation of cannabinoid CB1 receptor ligands.
journal_name
Behav Pharmacoljournal_title
Behavioural pharmacologyauthors
De Vry J,Jentzsch KRdoi
10.1097/01.fbp.0000087739.21047.d8subject
Has Abstractpub_date
2003-09-01 00:00:00pages
471-6issue
5-6eissn
0955-8810issn
1473-5849journal_volume
14pub_type
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