EFFECTS OF THE CANNABINOID CB1 RECEPTOR ANTAGONIST SR141716A ON THE BEHAVIOR OF PIGEONS AND RATS

SR141716A (Sanofi Recherche), a pyrazole derivative with high affinity for rat and human CBI cannabinoid receptors, has recently been report ed to reverse biochemical, physiological and behavioral effects induce d by cannabinoid agonists. The present experiments characterized the a ctivity of SR141716A (SR) in behavioral procedures designed to assess its antagonistic and intrinsic effects on unconditioned behavior and o n complex learned behaviors. Six adult male pigeons were trained to di scriminate injections of 0.56 mg/kg Delta(9)-tetrahydrocannabinol (Del ta(9)-THC) from vehicle under a two-key, fixed-ratio schedule of food reinforcement. SR (IM) produced a nearly complete blockade of THC-appr opriate responding occasioned by the training dose without inducing si gnificant changes in session response rates, but also produced partial substitution for Delta(9)-THC when administered alone. In another gro up of pigeons trained under a multiple schedule of signaled and unsign aled fixed consecutive number (FCN) responding, SR had little effect o n accuracy, but Delta(9)-THC produced dose-related decreases in accura cy under both schedule components. SR was also evaluated in acoustic s tartle procedures in rats. SR produced little effect either on startle amplitude or prepulse inhibition of acoustic startle. In contrast, th e potent cannabinomimetic CP-55,940 produced large decreases in startl e responses elicited by 120 dB [A] broad-band noise. These decreases w ere completely reversed by SR (10 mg/kg, IP). In concurrent measures, SR blocked the hypothermic effect CP-55, 940. These results suggest th at SR is an effective antagonist of the psychoactive effects of cannab inoids.