Cannabis use in humans has been associated with impairments in cognitive function, including deficits in the ability to focus, sustain and also shift attention. Using a rodent attentional set shifting task (ASST; Birrell et al 2000) we have demonstrated impairments in affective cognitive flexibility following acute administration of Δ⁹-tetrahydrocannabinol (THC) (Egerton et al., 2003). However, in humans a major concern is the potential for cognitive deficits arising from chronic use. The aim of the present study was to determine whether a chronic intermittent THC treatment regime would lead to deficits in executive function similar or different to those induced by acute treatment.

Male hooded Long Evans rats (250-300g, n=22-24/group) were administered THC (1mg/kg i.p.) or vehicle once per week for 4 weeks and tested in the ASST 30 minutes after the last dose of THC or vehicle. Rats performed a series of 2-choice discriminations digging for food reward in bowls differing in two perceptual dimensions (digging medium or odour). The ability to shift attention either within (intradimensional shift (IDS)) or between (extradimensional shift (EDS)) dimensions and the ability to reverse stimulus-reward associations was measured. Number of trials to criterion (6 consecutive correct digs) for the different groups were analysed using three way general linear model ANOVA for repeated measures, followed where appropriate by post-hoc analysis (student’s t test with Bonferroni correction).

Chronic intermittent THC produced significant deficits in the ability to shift attention both within [(IDS), trials to criterion: VEH: 8.22 ± 0.51, THC: 10.96 ± 0.75; p=0.005] and between [(EDS), trials to criterion: VEH: 9.41 ± 0.61, THC: 11.96 ± 0.68; p=0.008] perceptual dimensions in the ASST, as well as producing deficits in the first reversal discrimination in the task [(REV1), trials to criterion: VEH: 9.82 ± 0.40, THC: 12.52 ± 0.95; p=0.01]. THC treatment did not significantly affect performance in any of the other discriminations comprising the task.

The present results indicate that chronic intermittent THC treatment produces a different pattern of effects on performance of specific discriminations in this task compared to acute THC. In particular there is some tolerance to the acute deficits in reversal learning (deficits remain in only the most novel reversal discrimination, i.e. REV1), no tolerance to the acute deficit in IDS and also an emerging EDS deficit in the chronically treated rats. This indicates that the decreased affective flexibility and ability to focus attention to salient stimuli following acute administration of THC is maintained after chronic intermittent treatment, coupled with an emerging deficiency in the ability to effectively switch attention between perceptual dimensions in the task. THC-induced alterations in prefrontal circuitry may underlie these effects of chronic intermittent treatment on behavioural flexibility.

Birrell JM et al (2000). J. Neurosci. 20, 4320-4324.
Egerton A et al. (2003). Program number 110.15 2003 Abstract Viewer and Itinerary Planner. Washington, DC: Society for Neuroscience, 2003. Online.