Role of experience in acquisition and loss of tolerance to the effect of delta-9-THC on spaced responding.
Pharmacology, biochemistry, and behavior September 1976 DOI: 10.1016/0091-3057(76)90078-2 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Population | Albino rats |
| Interventions | delta-9-tetrahydrocannabinol (THC) THC vehicle |
| Dose | 4 mg/kg and 16 mg/kg |
| Duration | 12 days without behavioral testing, then testing on day 13; 1 week drug suspension in second phase |
| Topics | Cannabis |
| Key findings | THC sharply increased lever press rate in rats performing a DRL 30-second task, with effects stronger at 16 mg/kg than 4 mg/kg, and performance returned to baseline within 5 sessions. Prior THC exposure did not reduce the effect. The authors argue that performance in the drug state is a more important determinant of tolerance than drug exposure alone, and that continued task experience is needed for tolerance to be lost. |
Abstract
Albino rats were given extensive training in spaced responding, using a DRL 30 sec schedule of food reinforcement (only lever presses more than 30 sec apart were reinforced). All rats then went 12 days without behavioral testing. During this period half the rats received daily intragastric doses of delta-9-tetrahydrocannabinol (THC) and the rest equal volumes of the THC vehicle. On day 13, some rats received THC 3 hr before behavioral testing while others received only vehicle. The former showed a sharp increase in lever press rate over baseline levels, but the vehicle control rats were unaffected. The rats with 12 prior THC doses were no less affected than those with no previous drug history. Continued testing resulted in recovery of baseline performance within 5 sessions, again with no effect of previous drug history. Similar results were obtained with doses of 4 mg/kg and 16 mg/kg, though the drug's effects were more pronounced at the higher dose. These results demonstrate that performance in the drug state can be a far more important determinant of tolerance than mere exposure to THC. Drug administration was then suspended for 1 week. Rats that had become tolerant to 4 mg/kg THC were then redivided into 3 new groups. One group received daily doses of vehicle and DRL sessions, a second received DRL sessions without vehicle, and 1 group received neither vehicle nor DRL sessions for this week. Subsequent DRL testing after THC administration showed that only the groups receiving DRL sessions in the intervening week lost their previously acquired tolerance. Experience thus appears to play an important role in loss of tolerance to THC as well as in acquisition of tolerance.