Effect of repeated administration of delta 9-tetrahydrocannabinol on delayed matching-to-sample performance in rats

In the present study we examined the effect of repeated exposure to delta 9-tetrahydrocannabinol (THC) at a dose of 10 mg/kg (once a day for 4 days) 24 h after administration, on delayed matching-to-sample (DMTS) performance in rats using a three-lever operant apparatus. Although DMTS performance was not changed on the 1st day, it was impaired on the 2nd day. The impairment was potentiated in dependence of repeated administration. After withdrawal of THC, the impairment of DMTS performance gradually disappeared. On the 10th day after withdrawal, readministration of 10 mg/kg THC resulted in marked impairment of DMTS performance at 24 h after administration. Furthermore, a single administration of 1.0 mg/kg THC 30 min prior to the session, the dose at which a single administration did not cause impairment of DMTS performance in vehicle-treated rats, significantly decreased the number of reinforcements in the test trial. In conclusion, the present study demonstrated that repeated THC administration impaired DMTS performance under the condition of 24 h after administration, and that behavioral sensitization to this impairment developed. Furthermore, the suppressive state of lever-pressing induced by repeated THC administration may be a useful animal model for amotivational syndrome in humans.