Combined effects of THC and caffeine on working memory in rats

BACKGROUND AND PURPOSE Cannabis and caffeine are two of the most widely used psychoactive substances. Delta(9)-Tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, induces deficits in short-term memory. Caffeine, a non-selective adenosine receptor antagonist, attenuates some memory deficits, but there have been few studies addressing the effects of caffeine and THC in combination. Here, we evaluate the effects of these drugs using a rodent model of working memory. EXPERIMENTAL APPROACH Rats were given THC (0, 1 and 3 mg.kg(-1), i.p.) along with caffeine (0, 1, 3 and 10 mg.kg(-1), i.p.), the selective adenosine A(1)-receptor antagonist CPT (0, 3 and 10 mg.kg(-1)) or the selective adenosine A(2A)-receptor antagonist SCH58261 (0 and 5 mg.kg(-1)) and were tested with a delayed non-matching-to-position procedure in which behaviour during the delay was automatically recorded as a model of memory rehearsal. KEY RESULTS THC alone produced memory deficits at 3 mg.kg(-1). The initial exposure to caffeine (10 mg.kg(-1)) disrupted the established pattern of rehearsal-like behaviour, but tolerance developed rapidly to this effect. CPT and SCH58261 alone had no significant effects on rehearsal or memory. When a subthreshold dose of THC (1 mg.kg(-1)) was combined with caffeine (10 mg.kg(-1)) or CPT (10 mg.kg(-1)), memory performance was significantly impaired, even though performance of the rehearsal-like pattern was not significantly altered. CONCLUSION AND IMPLICATIONS Caffeine did not counteract memory deficits induced by THC but actually exacerbated them. These results are consistent with recent findings that adenosine A(1) receptors modulate cannabinoid signalling in the hippocampus.