Repeated, intermittent Δ9-tetrahydrocannabinol administration to rats impairs acquisition and performance of a test of visuospatial divided attention

The residual neuropsychological effects of marijuana abuse in man indicate a dysfunction of the attentional/executive systems. Moreover, experimental investigations suggest that repeated, intermittent (subchronic) Delta(9)-tetrahydrocannabinol (THC), the main psychoactive ingredient of marijuana, alters neurotransmission in the frontal cortex of rats and humans, a key neural site mediating attention and executive functions. In the present studies, the acquisition and performance of a test of visuospatial attention (the lateralized reaction time task) after subchronic THC administration (10.0 mg/kg twice daily for 14 days) was examined. Rats previously administered THC showed impairments in this self-paced version of the classic multiple-choice serial reaction time task, which persisted 14 days after the final drug administration. Longer time points were not examined. These attentional impairments were transiently reversible with an acute amphetamine (0.5 mg/kg) challenge. These behavioral data demonstrate that chronic THC administration to rats induces an attentional deficit, similar to that observed in humans who abuse marijuana. Finally, amphetamine's ability to reverse the attentional impairments provides indirect evidence that monoaminergic deficits may be linked to the cognitive dysfunction.