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 under 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 before and during daily dosing with Delta 9-THC (18 mg/kg/day). The dose-response curves for both Delta 9-THC and (R)-methanandamide were shifted to the right with daily dosing with Delta 9-THC, indicating tolerance to the effects of Delta 9-THC and cross-tolerance to the effects of (R)-methanandamide. 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 not consistently altered by daily Delta 9-THC administration. These results indicate that tolerance develops to the effects of Delta 9-THC, when Delta 9-THC is administered repeatedly. These results also indicate that cross-tolerance to (R)-methanandamide develops with repeated Delta 9-THC administration.
Lamb
R J
RJ
Departments of Psychiatry and Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, USA. lamb@uthscsa.edun
Järbe
T U
TU
Makriyannis
A
A
Lin
S
S
Goutopoulos
A
A
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D003216:Conditioning, Operant; D003913:Dextroamphetamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology*; D004347:Drug Interactions; D004361:Drug Tolerance; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077285:Rimonabant; D013997:Time Factors
D001095:Arachidonic Acids; D010880:Piperidines; D011720:Pyrazoles; C088155:methanandamide; D013759:Dronabinol; D000077285:Rimonabant; D003913:Dextroamphetamine