( R)-Methanandamide and Δ 9-tetrahydrocannabinol-induced operant rate decreases in rats are not readily antagonized by SR-141716A

Abstract

The current study examined the interaction between the cannabinoid CB 1 receptor agonists Δ 9-tetrahydrocannabinol and ( R)-methanandamide in combination with the cannabinoid CB 1 receptor antagonist SR-141716A ( N-(piperidin-1-yl)-5-(4-chloro-phenyl)-1-(2,4-dichlorophenyl)-4-methyl-1 H-pyrazole-3-carboxamide HCl) in rats responding for food on a fixed ratio (FR-10) schedule of food reinforcement. The study provided only limited evidence for antagonism by SR-141716A (at 1 mg/kg but not with 0.3, 3 and 10 mg/kg) of the rate suppressant effects induced by the cannabinoid CB 1 receptor agonist Δ 9-tetrahydrocannabinol (and only at the single dose of 5.6 mg/kg Δ 9-tetrahydrocannabinol). ( R)-Methanandamide in combination with SR-141716A resulted in a greater rate suppression compared to that induced by ( R)-methanandamide alone. Thus, SR-141716A augmented the rate-decreasing effects of ( R)-methanandamide and only minimally altered the rate-decreasing effects of Δ 9-tetrahydrocannabinol. Additionally, high doses (10 and 30 mg/kg) of SR-141716 singly consistently suppressed the rate of responding. The current results coupled with our previous data examining combinations of Δ 9-tetrahydrocannabinol or ( R)-methanandamide and SR-141716 (see text) underscore pharmacological/behavioral differences (whether quantitative or qualitative) between the cannabinoid CB 1 agonists ( R)-methanandamide and Δ 9-tetrahydrocannabinol revealed by their interactions with the cannabinoid CB 1 antagonist SR-141716.