Effects of Delta 9-tetrahydrocannabinol, (R)-methanandamide, SR 141716, and d-amphetamine before and during daily Delta 9-tetrahydrocannabinol dosing

We examined the effects of Delta 9-tetrahydrocannabinol (Delta 9-THC), (R)- (+)-arachidonyl-1'-hydroxy-2'-propylamide ((R)-methanandamide, AM 356), SR 141716, and d-amphetamine on fixed-ratio (FR) responding maintained by food in rats before and during daily dosing with Delta 9-THC. Rats responded un der a FR 10 schedule of food reinforcement. Cumulative dose-response curves for the various drugs were determined before and during daily Delta 9-THC administration. All four drugs dose-dependently decreased responding both b efore and during daily dosing with Delta 9-THC (18 mg/kg/day). The dose-res ponse curves for both Delta 9-THC and (R)-methanandamide were shifted to th e right with daily dosing with Delta 9-THC, indicating tolerance to the eff ects of Delta 9-THC and cross-tolerance to the effects of (R)-methanandamid e. The doses of d-amphetamine examined produced similar effects both before and during daily dosing with Delta 9-THC. The effects of SR 141716 were no t consistently altered by daily Delta 9-THC administration. These results i ndicate that tolerance develops to the effects of Delta 9-THC. when Delta 9 -THC is administered repeatedly. These results also indicate that cross-tol erance to (R)-methanandamide develops with repeated Delta 9-THC administrat ion. (C) 2000 Elsevier Science B.V. All rights reserved.