Factors influencing tolerance to the effects of delta9-THC on a conditioned avoidance response

Male, Fischer strain rats were resistant to the impairing effects of delta9--THC (15-60 mg/kg, IG) on performance of a conditioned pole-climb avoidance response (CAR) after daily subacute pretreatment for 4 or 6 days. A single administration of 20 mg/kg delta9--THC independent of the performance test did not attenuate the subsequent impairment caused by delta9--THC when tested 1-6 days later; however, administration 2 hr before each test attenuated the effect on subsequent tests given at intervals of 1-5 weeks. Similarly, subacute treatment with 20 mg/kg delta9--THC for 4 days independent of the performance test attenuated the impairment caused by delta9--THC during tests given to separate groups of rats 1 or 6, but not 14 days later. However, when the tests for tolerance were conducted repeatedly in the same rats, the attenuation appeared to persist for intervals up to 5 weeks. The results are discussed in terms of metabolic, functional and compensatory (behavioral) tolerance.