An attempt to correlate the development of tolerance to delta-9-tetrahydrocannabinol and d-amphetamine with their subcellular distribution in rat brain.
The daily application in rats of d-amphetamine during 4 weeks in increasing doses from 16-80 mg/kg/day developed a tolerance. The quantitative evaluation of the relative accumulation of unchanged d-amphetamine in different subcellular brain fractions estimated with 3H labelled d-amphetamine showed that the development of tolerance to amphetamine is not associated with a decreased accumulation of the unchanged drug in any subcellular fraction of the brain. Synthetic delta-9-tetrahydrocannabinol (THC) was injected (10 mg/kg) to rats twice daily. After the 9th injection the intensity of the initial depressant effect was approximately similar to that after one injection but completely disappeared after 3 hrs of treatment. The specific activities of delta-9-THC and its metabolites in brain subcellular fractions were estimated with use of 3H-delta-9-THC. The tolerance to delta-9-THC in contrast to amphetamine seems to be mainly metabolic.
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000648:ultrastructure*; D003913:Dextroamphetamine / Q000378:metabolism / Q000494:pharmacology*; D013759:Dronabinol / Q000378:metabolism / Q000494:pharmacology*; D004361:Drug Tolerance; D005260:Female; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D013347:Subcellular Fractions / Q000378:metabolism*; D013997:Time Factors
D013759:Dronabinol; D003913:Dextroamphetamine